| 1. |
- Brath, Ulrika, et al.
(author)
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Paramagnetic ligand tagging to identify protein binding sites
- 2015
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 137:35, s. 11391-11398
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Journal article (peer-reviewed)abstract
- Transient biomolecular interactions are the cornerstones of the cellular machinery. The identification of the binding sites for low affinity molecular encounters is essential for the development of high affinity pharmaceuticals from weakly binding leads but is hindered by the lack of robust methodologies for characterization of weakly binding complexes. We introduce a paramagnetic ligand tagging approach that enables localization of low affinity protein–ligand binding clefts by detection and analysis of intermolecular protein NMR pseudocontact shifts, which are invoked by the covalent attachment of a paramagnetic lanthanoid chelating tag to the ligand of interest. The methodology is corroborated by identification of the low millimolar volatile anesthetic interaction site of the calcium sensor protein calmodulin. It presents an efficient route to binding site localization for low affinity complexes and is applicable to rapid screening of protein–ligand systems with varying binding affinity.
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| 2. |
- Carlsson, Anna-Carin, 1976, et al.
(author)
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Halogen bonding in solution
- 2015
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In: Halogen Bonding II. Impact on Materials Chemistry and Life Sciences. Pierangelo Metrangolo, Giuseppe Resnati (eds.). - Cham : Springer. - 0340-1022 .- 1436-5049. - 9783319157313 ; 359, s. 49-76
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Book chapter (other academic/artistic)abstract
- Because of its expected applicability for modulation of molecular recognition phenomena in chemistry and biology, halogen bonding has lately attracted rapidly increasing interest. As most of these processes proceed in solution, the understanding of the influence of solvents on the interaction is of utmost importance. In addition, solution studies provide fundamental insights into the nature of halogen bonding, including, for example, the relative importance of charge transfer, dispersion, and electrostatics forces. Herein, a selection of halogen bonding literature is reviewed with the discussion focusing on the solvent effect and the electronic characteristics of halogen bonded complexes. Hence, charged and neutral systems together with two- and three-center bonds are presented in separate sub-sections. Solvent polarity is shown to have a slight stabilizing effect on neutral, two-center halogen bonds while strongly destabilizes charged, two-center complexes. It does not greatly influence the geometry of three-center halogen bonds, even though polar solvents facilitate dissociation of the counter-ion of charged three-center bonds. The charged three-center bonds are strengthened by increased environment polarity. Solvents possessing hydrogen bond donor functionalities efficiently destabilize all types of halogen bonds, primarily because of halogen vs hydrogen bond competition. A purely electrostatic model is insufficient for the description of halogen bonds in polar systems whereas it may give reasonable correlation to experimental data obtained in noninteracting, apolar solvents. Whereas dispersion plays a significant role for neutral, two-center halogen bonds, charged halogen bond complexes possess a significant charge transfer characteristic.
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| 3. |
- Lindblad, Sofia, et al.
(author)
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Halogen Bond Asymmetry in Solution
- 2018
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 140, s. 13503-13513
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Journal article (peer-reviewed)abstract
- © 2018 American Chemical Society. Halogen bonding is the noncovalent interaction of halogen atoms in which they act as electron acceptors. Whereas three-center hydrogen bond complexes, [D···H···D]+ where D is an electron donor, exist in solution as rapidly equilibrating asymmetric species, the analogous halogen bonds, [D···X···D]+, have been observed so far only to adopt static and symmetric geometries. Herein, we investigate whether halogen bond asymmetry, i.e., a [D-X···D]+ bond geometry, in which one of the D-X bonds is shorter and stronger, could be induced by modulation of electronic or steric factors. We have also attempted to convert a static three-center halogen bond complex into a mixture of rapidly exchanging asymmetric isomers, [D···X-D]+ ⇄ [D-X···D]+, corresponding to the preferred form of the analogous hydrogen bonded complexes. Using 15N NMR, IPE NMR, and DFT, we prove that a static, asymmetric geometry, [D-X···D]+, is obtained upon desymmetrization of the electron density of a complex. We demonstrate computationally that conversion into a dynamic mixture of asymmetric geometries, [D···X-D]+ r← [D-X···D]+, is achievable upon increasing the donor-donor distance. However, due to the high energetic gain upon formation of the three-center-four-electron halogen bond, the assessed complex strongly prefers to form a dimer with two static and symmetric three-center halogen bonds over a dynamic and asymmetric halogen bonded form. Our observations indicate a vastly different preference in the secondary bonding of H+ and X+. Understanding the consequences of electronic and steric influences on the strength and geometry of the three-center halogen bond provides useful knowledge on chemical bonding and for the development of improved halonium transfer agents.
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| 4. |
- Veiga, Alberte X., 1979, et al.
(author)
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N-arylation of protected azamacrocycles
- 2013
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In: Synthesis. - : Georg Thieme Verlag KG. - 0039-7881 .- 1437-210X. ; 45:6, s. 777-784
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Journal article (peer-reviewed)abstract
- A rapid method for efficient palladium-catalyzed N-arylation of polynitrogenated macrocycles is presented. Its applicability for functionalization of protected azamacrocycles of various sizes with substituted aryl bromides of optional electronic properties is demonstrated. The compatibility of the protocol with common N-protecting schemes as well as the impact of electronic versus steric factors is discussed. Using a commercially available catalytic system and easily available alkoxide or phenoxide base, the method provides moderate to excellent yields of N-arylated azamacrocycles (45-96%).
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