Electronic properties of a PrPC–Cu(<scp>ii</scp>) complex as a marker of 5-fold Cu(<scp>ii</scp>) coordination

Nowakowski, Michał; Czapla–Masztafiak, Joanna; Zhukov, Igor; Zhukova, Lilia; Kozak, Maciej; Kwiatek, Wojciech M.

doi:10.1039/c8mt00339d

Cited by 4 publications

(5 citation statements)

References 63 publications

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“…In the range of 20,012–20,016 eV, the unoccupied p and d states of Mo overlap with the p states of the ligands in all samples. In this energy region, multielectron transitions can occur from the Mo 1s state to ligand p states. , At the energy of 20,022 eV, the first main edge transition to the Mo 5p state is observed. Thereafter, the broad 1s → 5p transition is clearly visible.…”

Section: Resultssupporting

confidence: 55%

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Charge Distribution in Cationic Molybdenum Imido Alkylidene N-Heterocyclic Carbene Complexes: A Combined X-ray, XAS, XES, DFT, Mössbauer, and Catalysis Approach

et al. 2020

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The charge delocalization between the N-heterocyclic carbene (NHC) and the metal in cationic molybdenum imido alkylidene NHC mono(nonafluoro-tert-butoxide) complexes has been studied for different NHCs, i.e., 1,3-dimesitylimidazol-2ylidene (IMes), 1,3-dimesityl-4,5-dichloroimidazol-2-ylidene (IM-esCl 2 ), 1,3-dimesityl-4,5-dimethylimidazol-2-ylidene (IMesMe 2 ), and 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene (IMesH 2 ). The binding situation in the corresponding cationic complexes Mo(N-2,6-Me 2 C 6 H 3 )(CHCMe 2 Ph)(NHC)(OC(CF 3 ) 3 ) + B(Ar F ) 4 − (NHC = IMes (1), IMesCl 2 (2), IMesMe 2 (3), and IMesH 2 (4) was compared to that of the analogous neutral Schrock catalyst Mo(N-2,6-Me 2 C 6 H 3 )(CHCMe 2 Ph)((OC(CF 3 ) 3 )) 2 (5). Singlecrystal X-ray data were used as a starting point for the optimization of the geometries of the catalysts at the PBE0-D3BJ/def2-SVP level of theory; the obtained data were compared to those obtained from X-ray absorption (XAS) and emission spectroscopy (XES). The very similar X-ray spectroscopic signatures of the XANES (X-ray absorption near-edge structure) and Kβ-XES of catalysts 1, 2, and 5 suggest that a similar oxidation state and charge are present at the Mo center in all three cases. However, charge delocalization is more pronounced in 1 and 2 compared to 5. This is supported by quantum chemical (QC) calculations, which reveal that all NHCs compensate to a very similar extent for the cationic charge at molybdenum, leading to charge model 5 (CM5) partial charges at Mo between +1.292 and +1.298. Accordingly, the partial charge in the NHCs was in the range of +0.486 to +0.515. This strong delocalization of the positive charge in cationic molybdenum imido alkylidene NHC (nonafluoro-tert-butoxide) complexes is also illustrated by the finding that the analogous neutral Schrock catalyst 5 has a more positive charge at molybdenum (+1.435) despite being a neutral 14-electron complex. Complementarily, charge analysis on complexes 1 and 2 and the acetonitrilecontaining derivatives 1•MeCN and 2•MeCN revealed that a small partial positive charge of about +0.1 was found on acetonitrile, accompanied by an increase in positive charge on Mo. Accordingly, the partial charges at the imido, the alkoxide, and NHC ligands decreased slightly. Finally, the catalytic activity of complexes 1−4 was determined for a number of purely hydrocarbon-based substrates in a set of olefin metathesis reactions. A correlation of the Tolman electronic parameter (TEP) with catalyst activity, expressed as the turnover frequency after 3 min, TOF 3min , was found for complexes 1−3 based on imidazol-2-ylidenes. 57 Fe-Mossbauer measurements on Mo(N-2,6-Me 2 C 6 H 3 )(CH-ferrocenyl)(NHC)(OTf) 2 and Mo(N-2,6-Me 2 C 6 H 3 )(CH-ferrocenyl)-(NHC)(OTf) + B(Ar F ) 4− (NHC = IMes (6, 8) and IMesH 2 (7, 9)) revealed significant changes in the quadrupole splitting of these complexes. These suggest a significantly more efficient charge distribution between the cationic molybdenum center and an imidazol-2-ylidene-based NHC compared t...

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Section: Resultssupporting

confidence: 55%

“…In this energy region, multielectron transitions can occur from the Mo 1s state to ligand p states. 27,28 At the energy of 20,022 eV, the first main edge transition to the Mo 5p state is observed. Thereafter, the broad 1s → 5p transition is clearly visible.…”

Section: ■ Results and Discussionmentioning

confidence: 98%

Charge Distribution in Cationic Molybdenum Imido Alkylidene N-Heterocyclic Carbene Complexes: A Combined X-ray, XAS, XES, DFT, Mössbauer, and Catalysis Approach

et al. 2020

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“…It thereby resembles the CD spectrum for left-handed twisted antiparallel β-sheets 77 , as well as the CD spectrum for a hydrophobic fragment of the Aβ peptide, i.e. Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), to which we previously have attributed an antiparallel β-sheet secondary structure 75 . We therefore argue that binding of Cu(II) ions to the OR peptide in water results in formation of antiparallel βsheet structures.…”

Section: Solution Structure Of the Or Peptidementioning

confidence: 52%

“…The PrP C protein binds up to six different types of divalent metal ions, including Cu(II), Zn(II), Ni(II), and Mn(II), by two distinct domains with different metal ion affinities [26][27][28] . The octarepeat (OR) region is located in the N-terminal domain where it spans residues 60-91 (Fig.…”

Section: Introductionmentioning

confidence: 99%

The Prion Protein Octarepeat Domain Forms Transient β-sheet Structures Upon Residue-Specific Cu(II) and Zn(II) Binding

Gielnik

Szymańska

Jarvet

et al. 2021

Preprint

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Misfolding of the cellular prion protein (PrPC) is associated with the development of fatal neurodegenerative diseases called transmissible spongiform encephalopathies (TSEs). Metal ions appear to play a crucial role in the protein misfolding, and metal imbalance may be part of TSE pathologies. PrPC is a combined Cu(II) and Zn(II) metal binding protein, where the main metal binding site is located in the octarepeat (OR) region. Here, we used biophysical methods to characterize Cu(II) and Zn(II) binding to the isolated OR region. Circular dichroism (CD) spectroscopy data suggest that the OR domain binds up to four Cu(II) ions or two Zn(II) ions. Upon metal binding, the OR region seems to adopt a transient antiparallel β-sheet hairpin structure. Fluorescence spectroscopy data indicates that under neutral conditions, the OR region can bind both Cu(II) and Zn(II) ions, whereas under acidic conditions it binds only Cu(II) ions. Molecular dynamics simulations suggest that binding of both metal ions to the OR region results in formation of β-hairpin structures. As formation of β-sheet structures is a first step towards amyloid formation, we propose that high concentrations of either Cu(II) or Zn(II) ions may have a pro-amyloid effect in TSEs.

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“…The PrP C protein is known to bind up to six different types of divalent metal ions, including Cu(II), Zn(II), Ni(II), and Mn(II), by two distinct domains with different metal ion affinities. − The octarepeat (OR) region is located in the N-terminal domain, where it spans residues 60–91 (Figure ). It contains four tandem PHGGGWGQ repeats and binds Cu(II), Zn(II), and Ni(II) ions with strong affinity (around 0.1 nM for Cu(II), 10 nM for Ni(II), and 400 nM for Zn(II)).…”

Section: Introductionmentioning

confidence: 99%

Prion Protein Octarepeat Domain Forms Transient β-Sheet Structures upon Residue-Specific Binding to Cu(II) and Zn(II) Ions

et al. 2023

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Misfolding of the cellular prion protein (PrPC) is associated with the development of fatal neurodegenerative diseases called transmissible spongiform encephalopathies (TSEs). Metal ions appear to play a crucial role in PrPC misfolding. PrPC is a combined Cu(II) and Zn(II) metal-binding protein, where the main metal-binding site is located in the octarepeat (OR) region. Thus, the biological function of PrPC may involve the transport of divalent metal ions across membranes or buffering concentrations of divalent metal ions in the synaptic cleft. Recent studies have shown that an excess of Cu(II) ions can result in PrPC instability, oligomerization, and/or neuroinflammation. Here, we have used biophysical methods to characterize Cu(II) and Zn(II) binding to the isolated OR region of PrPC. Circular dichroism (CD) spectroscopy data suggest that the OR domain binds up to four Cu(II) ions or two Zn(II) ions. Binding of the first metal ion results in a structural transition from the polyproline II helix to the β-turn structure, while the binding of additional metal ions induces the formation of β-sheet structures. Fluorescence spectroscopy data indicate that the OR region can bind both Cu(II) and Zn(II) ions at neutral pH, but under acidic conditions, it binds only Cu(II) ions. Molecular dynamics simulations suggest that binding of either metal ion to the OR region results in the formation of β-hairpin structures. As the formation of β-sheet structures can be a first step toward amyloid formation, we propose that high concentrations of either Cu(II) or Zn(II) ions may have a pro-amyloid effect in TSE diseases.

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Electronic properties of a PrPC–Cu(ii) complex as a marker of 5-fold Cu(ii) coordination

Abstract: The full scale huPrPC–Cu(ii) protein complex was a subject of Cu K-edge XAS study. Two Cu(ii) binding sites structures were obtained and a stabilizing charge transfer effect was identified.

Cited by 4 publications

References 63 publications

Charge Distribution in Cationic Molybdenum Imido Alkylidene N-Heterocyclic Carbene Complexes: A Combined X-ray, XAS, XES, DFT, Mössbauer, and Catalysis Approach

Charge Distribution in Cationic Molybdenum Imido Alkylidene N-Heterocyclic Carbene Complexes: A Combined X-ray, XAS, XES, DFT, Mössbauer, and Catalysis Approach

The Prion Protein Octarepeat Domain Forms Transient β-sheet Structures Upon Residue-Specific Cu(II) and Zn(II) Binding

Prion Protein Octarepeat Domain Forms Transient β-Sheet Structures upon Residue-Specific Binding to Cu(II) and Zn(II) Ions

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