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von der Heiden, D., Vanderkooy, A. & Erdélyi, M. (2020). Halogen bonding in solution: NMR spectroscopic approaches. Coordination chemistry reviews, 407, Article ID 213147.
Open this publication in new window or tab >>Halogen bonding in solution: NMR spectroscopic approaches
2020 (English)In: Coordination chemistry reviews, ISSN 0010-8545, E-ISSN 1873-3840, Vol. 407, article id 213147Article, review/survey (Refereed) Published
National Category
Organic Chemistry Physical Chemistry
Identifiers
urn:nbn:se:uu:diva-407480 (URN)10.1016/j.ccr.2019.213147 (DOI)000514240000003 ()
Funder
Vinnova, 2019-02160Swedish Research Council Formas, 2017-0009Swedish Research Council, 2016-03602
Available from: 2020-03-25 Created: 2020-03-25 Last updated: 2020-03-25Bibliographically approved
Dickman, R., Danelius, E., Mitchell, S. A., Hansen, D. F., Erdélyi, M. & Tabor, A. B. (2019). A Chemical Biology Approach to Understanding Molecular Recognition of Lipid II by Nisin(1-12): Synthesis and NMR Ensemble Analysis of Nisin(1-12) and Analogues. Chemistry - A European Journal, 25(64), 14572-14582
Open this publication in new window or tab >>A Chemical Biology Approach to Understanding Molecular Recognition of Lipid II by Nisin(1-12): Synthesis and NMR Ensemble Analysis of Nisin(1-12) and Analogues
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2019 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 25, no 64, p. 14572-14582Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2019
Keywords
antibiotics, cyclic peptides, lantibiotics, NMR spectroscopy, solid phase synthesis
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-399097 (URN)10.1002/chem.201902814 (DOI)000489322000001 ()31599485 (PubMedID)
Funder
Swedish Research Council, 2016:03602Wellcome trust, 101569/z/13/z
Available from: 2019-12-13 Created: 2019-12-13 Last updated: 2019-12-13Bibliographically approved
Nyandoro, S. S., Maeda, G., Munissi, J. J. E., Gruhonjic, A., Fitzpatrick, P. A., Lindblad, S., . . . Erdélyi, M. (2019). A New Benzopyranyl Cadenane Sesquiterpene and Other Antiplasmodial and Cytotoxic Metabolites from Cleistochlamys kirkii. Molecules, 24(15), Article ID 2746.
Open this publication in new window or tab >>A New Benzopyranyl Cadenane Sesquiterpene and Other Antiplasmodial and Cytotoxic Metabolites from Cleistochlamys kirkii
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2019 (English)In: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 24, no 15, article id 2746Article in journal (Refereed) Published
Abstract [en]

Phytochemical investigations of ethanol root bark and stem bark extracts of Cleistochlamys kirkii (Benth.) Oliv. (Annonaceae) yielded a new benzopyranyl cadinane-type sesquiterpene (cleistonol, 1) alongside 12 known compounds (2-13). The structures of the isolated compounds were established from NMR spectroscopic and mass spectrometric analyses. Structures of compounds 5 and 10 were further confirmed by single crystal X-ray crystallographic analyses, which also established their absolute stereochemical configuration. The ethanolic crude extract of C. kirkii root bark gave 72% inhibition against the chloroquine-sensitive 3D7-strain malaria parasite Plasmodium falciparum at 0.01 mu g/mL. The isolated metabolites dichamanetin, (E)-acetylmelodorinol, and cleistenolide showed IC50 = 9.3, 7.6 and 15.2 mu M, respectively, against P. falciparum 3D7. Both the crude extract and the isolated compounds exhibited cytotoxicity against the triple-negative, aggressive breast cancer cell line, MDA-MB-231, with IC50 = 42.0 mu g/mL (crude extract) and 9.6-30.7 mu M (isolated compounds). Our findings demonstrate the potential applicability of C. kirkii as a source of antimalarial and anticancer agents.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
Cleistochlamys kirkii, Annonaceae, benzopyranyl sesquiterpene, cleistonol, antiplasmodial activity, malaria, cytotoxicity
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-393825 (URN)10.3390/molecules24152746 (DOI)000482441100069 ()31362371 (PubMedID)
Funder
Swedish Research Council, 2016-05857Australian Research Council, LP120200557Swedish Research Council
Available from: 2019-10-01 Created: 2019-10-01 Last updated: 2019-10-01Bibliographically approved
Peng, C., Atilaw, Y., Wang, J., Xu, Z., Poongavanam, V., Shi, J., . . . Erdélyi, M. (2019). Conformation of the Macrocyclic Drug Lorlatinib in Polar and Nonpolar Environments: A MD Simulation and NMR Study. ACS Omega, 4(26), 22245-22250
Open this publication in new window or tab >>Conformation of the Macrocyclic Drug Lorlatinib in Polar and Nonpolar Environments: A MD Simulation and NMR Study
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2019 (English)In: ACS Omega, E-ISSN 2470-1343, Vol. 4, no 26, p. 22245-22250Article in journal (Refereed) Published
Abstract [en]

The replica exchange molecular dynamics (REMD) simulation is demonstrated to readily predict the conformations of the macrocyclic drug lorlatinib, as validated by solution NMR studies. In aqueous solution, lorlatinib adopts a conformer identical to its target bound structure. This conformer is stabilized by an extensive hydrogen bond network to the solvents. In chloroform, lorlatinib populates two conformers with the second one being less polar, which may contribute to lorlatinib’s ability to cross cell membranes.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-401136 (URN)10.1021/acsomega.9b03797 (DOI)000504635000068 ()31891108 (PubMedID)
Note

De 2 första författarna delar förstaförfattarskapet

Available from: 2020-01-07 Created: 2020-01-07 Last updated: 2020-01-28Bibliographically approved
Dalenius, E., Ohm, R. G., Ahsanullah, A., Ong, H., Chemtob, S., Erdélyi, M. & D. Lubell, W. (2019). Dynamic Chirality in the Mechanism of Action of Allosteric CD36 Modulators of Macrophage-Driven Inflammation. Journal of Medicinal Chemistry, 62(24), 111071-11079
Open this publication in new window or tab >>Dynamic Chirality in the Mechanism of Action of Allosteric CD36 Modulators of Macrophage-Driven Inflammation
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2019 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 62, no 24, p. 111071-11079Article in journal (Refereed) Published
Abstract [en]

Dynamic chirality influences numerous processes in nature from protein folding to catalysis. Azapeptides are peptidomimetics possessing semicarbazide residues that can interconvert between sp2 and sp3 hybridization, resulting in stereodynamic interconversions of pseudo-R and -S-configurations by means of a planar intermediate. Cyclic azapeptides have shown unprecedented binding affinity to the cluster of differentiation 36 receptor (CD36) and ability to mitigate macrophage-driven inflammation by modulation of the toll-like receptor 2/6 pathway. A novel approach to synthesize cyclic peptides via A3-macrocyclization has been used to make R- and S-configuration controls to study the relevance of semicarbazide hybridization for modulator activity. Nuclear magnetic resonance spectroscopy analysis of potent cyclic azapeptide CD36 modulators (e.g., 1 and 2) and related cyclic peptides demonstrated that binding affinity correlated with conformational rigidity, and a hybridization preference for sp2 > S- > R-sp3 semicarbazide nitrogen configuration was evaluated. Evidence of the active conformation and the relevance for dynamic chirality serve as insights for creating cyclic (aza)peptide CD36 modulators to curb inflammation.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-401236 (URN)10.1021/acs.jmedchem.9b00918 (DOI)000505633400009 ()31774287 (PubMedID)
Funder
Swedish Research Council, 201603602
Available from: 2020-01-07 Created: 2020-01-07 Last updated: 2020-01-28Bibliographically approved
Vanderkooy, A., Gupta, A. K., Foldes, T., Lindblad, S., Orthaber, A., Papai, I. & Erdélyi, M. (2019). Halogen Bonding Helicates Encompassing Iodonium Cations. Angewandte Chemie International Edition, 58(27), 9012-9016
Open this publication in new window or tab >>Halogen Bonding Helicates Encompassing Iodonium Cations
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2019 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 58, no 27, p. 9012-9016Article in journal (Refereed) Published
Abstract [en]

The first halonium-ion-based helices were designed and synthesized using oligo-aryl/pyridylene-ethynylene backbones that fold around reactive iodonium ions. Halogen bonding interactions stabilize the iodonium ions within the helices. Remarkably, the distance between two iodonium ions within a helix is shorter than the sum of their van der Waals radii. The helical conformations were characterized by X-ray crystallography in the solid state, by NMR spectroscopy in solution and corroborated by DFT calculations. The helical complexes possess potential synthetic utility, as demonstrated by their ability to induce iodocyclization of 4-penten-1-ol.

Place, publisher, year, edition, pages
WILEY-V C H VERLAG GMBH, 2019
Keywords
3c-4e bonds, halocyclization, halogen bonds, helices, iodonium ions
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-391952 (URN)10.1002/anie.201904817 (DOI)000476691200005 ()31074942 (PubMedID)
Funder
Swedish Research Council Formas, 2017-01173
Available from: 2019-08-28 Created: 2019-08-28 Last updated: 2019-08-28Bibliographically approved
Reiersolmoen, A. C., Csokas, D., Papai, I., Fiksdahl, A. & Erdélyi, M. (2019). Mechanism of Au(III)-Mediated Alkoxycyclization of a 1,6-Enyne. Journal of the American Chemical Society, 141(45), 18221-18229
Open this publication in new window or tab >>Mechanism of Au(III)-Mediated Alkoxycyclization of a 1,6-Enyne
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2019 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 141, no 45, p. 18221-18229Article in journal (Refereed) Published
Abstract [en]

Gold-mediated homogeneous catalysis is a powerful tool for construction of valuable molecules and has lately received growing attention. Whereas Au(I)-catalyzed processes have become well established, those mediated by Au(III) have so far barely been explored, and their mechanistic understanding remains basic. Herein, we disclose the combined NMR spectroscopic, single-crystal X-ray crystallographic, and computational (DFT) investigation of the Au(III)-mediated alkoxycyclization of a 1,6-enyne in the presence of a bidentate pyridine-oxazoline ligand. The roles of the counterion, the solvent, and the type of Au(III) complex have been assessed. Au(III) is demonstrated to be the active catalyst in alkoxycyclization. Alkyne coordination to Au(III) involves decoordination of the pyridine nitrogen and is the rate-limiting step.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2019
National Category
Organic Chemistry Physical Chemistry
Identifiers
urn:nbn:se:uu:diva-400015 (URN)10.1021/jacs.9b09108 (DOI)000498281600035 ()31618010 (PubMedID)
Available from: 2019-12-19 Created: 2019-12-19 Last updated: 2020-01-09Bibliographically approved
Erdélyi, M. (2019). The three-center halogen bond. In: : . Paper presented at 34. Organisk Kjemisk Vintermøte, 10. - 13. januar 2019, Skeikampen, Norge.
Open this publication in new window or tab >>The three-center halogen bond
2019 (English)Conference paper, Oral presentation with published abstract (Refereed)
Abstract [en]

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

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

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

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

National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-373611 (URN)
Conference
34. Organisk Kjemisk Vintermøte, 10. - 13. januar 2019, Skeikampen, Norge
Available from: 2019-01-15 Created: 2019-01-15 Last updated: 2019-09-25Bibliographically approved
Lindblad, S., Mehmeti, K. & Erdélyi, M. (2018). Asymmetric [N-X-N]+ Halogen Bonds in Solution. In: : . Paper presented at 1ST NATIONAL MEETING OF THE SWEDISH CHEMICAL SOCIETY in Lund, 17-20 June 2018.
Open this publication in new window or tab >>Asymmetric [N-X-N]+ Halogen Bonds in Solution
2018 (English)Conference paper, Poster (with or without abstract) (Other academic)
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-357744 (URN)
Conference
1ST NATIONAL MEETING OF THE SWEDISH CHEMICAL SOCIETY in Lund, 17-20 June 2018
Available from: 2018-08-20 Created: 2018-08-20 Last updated: 2018-08-22Bibliographically approved
Begum, S., Nyandoro, S., Buriyo, A., Makangara, J., Munissi, J., Duffy, S., . . . Erdelyi, M. (2018). Bioactivities of extracts, debromolaurintrerol and fucosterol from Macroalgae species. Tanzania Journal of Science, 44(2), 104-116
Open this publication in new window or tab >>Bioactivities of extracts, debromolaurintrerol and fucosterol from Macroalgae species
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2018 (English)In: Tanzania Journal of Science, ISSN 2507-7961, Vol. 44, no 2, p. 104-116Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Dar es Salaam: , 2018
Keywords
Macrolgae, antiplasmodial, antimicrobial, antioxidant, cytotoxicity, DPPH radical scavenging, debromolaurinterol and fucosterol
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-355944 (URN)
Available from: 2018-07-09 Created: 2018-07-09 Last updated: 2019-01-08Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-0359-5970

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