| 1. |
- Krasikova, Raisa, et al.
(author)
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Synthesis and Preclinical Evaluation of 6-[18F]Fluorine-α-methyl-l-tryptophan, a Novel PET Tracer for Measuring Tryptophan Uptake
- 2020
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In: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 11:12, s. 1756-1761
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Journal article (peer-reviewed)abstract
- The positron emission tomography (PET) radioligand α-[11C]methyl-l-tryptophan ([11C]AMT) has been used to assess tryptophan metabolism in cancer, epilepsy, migraine, and autism. Despite its extensive application, the utility of this tracer is currently hampered by the short half-life of the radionuclide used for its labeling (11C, t1/2 = 20.4 min). We herein report the design, synthesis, radiolabeling, and initial in vivo evaluation of a fluorine-18 (18F, t 1/2 = 109.7 min) labeled analogue that is fluorinated in the 6-position of the aromatic ring ([18F]6-F-AMTr). In a head-to-head comparison between [18F]6-F-AMTr and [11C]AMT in mice using PET, peak brain radioactivity, regional brain distribution, and kinetic profiles were similar between the two tracers. [18F]6-F-AMTr was however not a substrate for IDO1 or TPH as determined in in vitro enzymatic assays. The brain uptake of the tracer is thus more likely related to LAT1 transport over the blood-brain barrier than metabolism along the serotonin or kynurenine pathways.
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| 2. |
- Johnson, Magnus, et al.
(author)
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Mechanisms of the CO2 Insertion into (PCP) Palladium Allyl and Methyl sigma-Bonds. A Kinetic and Computational Study
- 2010
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In: Organometallics. - : American Chemical Society (ACS). - 0276-7333 .- 1520-6041. ; 29:16, s. 3521-3529
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Journal article (peer-reviewed)abstract
- The reaction of the sigma-bonded (PCP)Pd-Me complex (PCP = 2,6-bis[(di-tert-butylphosphino)methyl]phenyl) with CO2 is first-order in palladium and first-order in CO, with a rate constant k(s) = 8.9 +/- 0.8 M-1 s(-1) at 353 K. Activation parameters are Delta H double dagger = 73 7 kJ/mol and Delta S double dagger = 118 +/- 19 J/K mol. Based on this and theoretical calculations we propose an S(E)2 mechanism where the coordinated methyl group attacks a completely noncoordinated carbon dioxide molecule in a bimolecular reaction. The PCPPd-crotyl complex was synthesized in an 65:35 E:Z mixture, and it was shown to react with CO, to give the complex PCPPd-O(CO)CH(CH3)CHCH2 as a single isomer, where the former gamma-carbon has been carboxylated. Theoretical calculations again suggest an S(E)2 mechanism with a noncoordinated carbon dioxide reacting with the terminal carbon on the allyl group, forming an eta(2)-bonded olefin complex as an intermediate. The rearrangement of this intermediate to the O-bonded product is concluded to be rate determining. The crystal structure of PCPPd-O(CO)C(CH3)(2)CHCH2 is reported and as well as the solubility of carbon dioxide in benzene-d(6) at different pressures and temperatures.
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| 3. |
- Kondrashov, Mikhail
(author)
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C–H activation through late transition metal cyclometallation. Addressing selectivity and reactivity problems.
- 2015
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Doctoral thesis (other academic/artistic)abstract
- The ligand-directed C—H activation relies on a coordinating donor atom being in proximity to the C—H bond activated. Cyclometallation of 2-(1-naphthyl)-pyridine – a substrate containing both γ- and δ-positions in proximity to the directing nitrogen atom – was studied. Cycloruthenation and cyclopalladation result in γ-substitution and formation of the corresponding 5-membered metallacycles, which is in agreement with published regioselectivities of the corresponding catalytic reactions. Simultaneously, cycloauration and cycloborylation result in δ-substitution and formation of the corresponding 6-membered metallacycles. X-ray structures of all the metallacycles are presented. Deuterium labelling studies show that the cyclopalladation and cycloauration are irreversible, while the cycloruthenation is reversible and happens in both γ- and δ-positions. Attempts to synthesise bimetallic palladium complexes, consisting of two (2-phenyl-pyridine) palladium fragments connected via bridging ligands, resulted predominantly in the formation of monometallic species. While 1,8-naphthyridine and 7-aza-indole bind to palladium in an L-fashion with only one of the two nitrogen atoms, N-piperidine dithiocarbamic acid binds with both sulfur atoms in a chelating, rather than a bridging fashion. 3,3-Dimethylglutaric acid acts as a bridging ligand. X-ray structures of naphthyridine and dithiocarbamate complexes are presented. No increase in the reactivity is observed, when 1,8-naphthyridine, 7-aza-indole and N-piperidine dithiocarbamic acid were used as additives in palladium-catalysed acetoxylation and bromination of 2-phenyl-pyridine. Oxidative anion metathesis was employed as a method of synthesis of organic salts. Trimethylsulfoxonium iodide salts can be converted to tetrafluoroborate, hexafluorophosphate, trifluoroacetate, tosylate and bis-triflimide salts in the presence of hydrogen peroxide and the corresponding acids. The scope of cations, suitable for this reaction also includes N-alkylpyridinium and quaternary phosphonium salts. N-acetoxypyridinium chloride was employed as an oxidant in the palladium-catalysed C—H functionalisation of 2-aryl-pyridine resulting in the formation of the corresponding chloro-derivative. Trimethylsulfoxonium tetrafluoroborate, hexafluorophosphate and tosylate are unreactive as oxidants towards 2-(phenyl)-pyridine palladium acetate. Cyclopalladation of PCP pincer ligands with aromatic and aliphatic backbones by (PhCN)2PdCl2 was shown to proceed at temperatures as low as -62⁰C. The initial interaction results in the formation of a mixture of coordinated species, only some of which react further to form metallacyclic pincer compounds. The formation of pre-cyclometallation intermediates is kinetically disfavoured. However, C—H activation is fast and not rate-limiting in case of neither sp2 nor sp3 C—H bonds.
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| 4. |
- Kondrashov, Mikhail, et al.
(author)
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Crystal structure of (piperidine-1-carbo-di-thio-ato-κ(2) S,S)[2-(pyridin-2-yl)phenyl-κ(2) C (1),N]palladium(II).
- 2015
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In: Acta crystallographica. Section E: Crystallographic communications. - 2056-9890. ; 71:Pt 9, s. 166-166
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Journal article (peer-reviewed)abstract
- The title compound, [Pd(C11H8N)(C6H10NS2)], crystallizes with three similar and discrete mol-ecules in the asymmetric unit. The CNS2 donor set defines a distorted square-planar geometry around the Pd(II) atom, with very small deviations from planarity. The bidentate nature of the ligands gives fairly large deviations from the ideal 90° angles; the C-Pd-N angles are all around 81° and the S-Pd-S angles are around 75°. Mol-ecules pack via dispersion inter-actions.
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| 5. |
- Kondrashov, Mikhail, et al.
(author)
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Cyclometallated phenyl-pyridine palladium species. Monomeric complex formation with potentially bridging ligands
- 2016
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In: Inorganica Chimica Acta. - : Elsevier BV. - 0020-1693. ; 443, s. 136-140
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Journal article (peer-reviewed)abstract
- The cyclometallated dinuclear (2-phenyl-pyridine) palladium acetate and chloride [{PdCl(phpy)}(2)] and [{PdOAc(phpy)}(2)] were reacted with potentially bridging N- and S-donor ligands. The N,N-ligands bind with only one nitrogen and form monomeric products. The S,S-ligand binds in a chelate mode, also forming a monomeric complex. 3,3-Dimethyl glutarate, on the other hand, binds in a bridging mode. An X-ray structure of the complex with naphthyridine is presented. (C) 2016 Elsevier B.V. All rights reserved.
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| 6. |
- Kondrashov, Mikhail, et al.
(author)
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Metal controlled regioselectivity in the cyclometallation of 2-(1-naphthyl)-pyridine.
- 2015
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In: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1364-548X .- 1359-7345. ; 51:5, s. 911-913
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Journal article (peer-reviewed)abstract
- Cyclometallation of 2-(1-naphthyl)-pyridine is described. While cyclopalladation results in a five-membered metallacycle, cycloauration displays a completely orthogonal regioselectivity, resulting in the six-membered ring analogue. Bromination of the gold metallacycle results in the new C-H functionalisation product 2-(8-bromonaphth-1-yl)pyridine.
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| 7. |
- Kondrashov, Mikhail, et al.
(author)
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Multiple Applications of a Novel Biarsenical Imaging Probe in Fluorescence and PET Imaging of Melanoma
- 2021
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In: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 32:3, s. 497-501
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Journal article (peer-reviewed)abstract
- A new fluorescent biarsenical peptide labeling probe was synthesized and labeled with the radioactive isotopes C-11 and F-18. The utility of this probe was demonstrated by installing each of these isotopes into a melanocortin 1 receptor (MC1R) binding peptide, which targets melanoma tumors. Its applicability was further showcased by subsequent in vitro imaging in cells as well as in vivo imaging in melanoma xenograft mice by fluorescence and positron emission tomography.
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| 8. |
- Kondrashov, Mikhail, et al.
(author)
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Regioselectivity in C-H activation: reagent control in cyclometallation of 2-(1-naphthyl)-pyridine.
- 2016
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In: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9234 .- 1477-9226. ; 45:2, s. 525-531
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Journal article (peer-reviewed)abstract
- 2-(1-Naphthyl)-pyridine () possesses sp(2) C-H bonds in both the γ- and δ-positions and is therefore a suitable substrate for studying the cyclometallation selectivity with different reagents and conditions. Such selectivity studies are reported. Based on deuterium-exchange experiments it is concluded that cycloruthenation with RuCl2(p-cymene) dimer is reversible with kinetic and thermodynamic preference for γ-substitution. Electrophilic cycloborylation, on the other hand, shows unusual δ-substitution. The previously published cyclopalladation and cycloauration of the substrate was studied in detail and was shown to be irreversible; they proceed under kinetic control and give γ- and δ-substitution for palladium and gold, respectively.
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| 9. |
- Mousa, Abdelrazek H., et al.
(author)
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Aromatic PCN pincer palladium complexes : Forming and breaking CC bonds
- 2017
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In: Journal of Organometallic Chemistry. - : Elsevier BV. - 0022-328X. ; 845, s. 157-164
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Journal article (peer-reviewed)abstract
- Through a salt metathesis reaction, ( t-BuPCN)Pd-ONO2 (2) was prepared and used as a precursor for producing ( t-BuPCN)Pd-OH (3) and ( t-BuPCN)Pd-aryl acetylide complexes 4 (phenyl acetylide) and 5 (p-tolyl acetylide). The aryl acetylide complexes could also be prepared through another synthetic route: by condensation of 3 with the corresponding aryl acetylene. The reactivity of complexes 3 and 4 toward carbon dioxide was studied and it was found that both reactions give the hydrogen carbonate complex (6). The low reactivity of the Pd-acetylide bond was further confirmed by the fact that the propiolate complex undergoes decarboxylation to give 4. PCN palladium complexes are good catalysts for the decarboxylative cross coupling reactions between acetylene carboxylic acids and aryl halides. The yield of the cross coupling product was improved by adding a catalytic amount of CuI.
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