Showing papers by "James Alexis Platts published in 2019"
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TL;DR: The importance of noncoordinative adducts in modulating the AQP3 inhibition properties of the investigated Au(III) compounds has been elucidated, and these interactions should be further considered in the future design of isoform-selective AQP inhibitors.
Abstract: A series of six new Au(III) coordination compounds with phenanthroline ligands have been synthesized and studied for the inhibition of the water and glycerol channel aquaporin-3 (AQP3). From a combination of different experimental and computational approaches, further insights into the mechanisms of AQP3 inhibition by gold compounds at a molecular level have been gained. The results evidence the importance of noncoordinative adduct formation, prior to “covalent” protein binding, to achieve selective AQP3 inhibition.
29 citations
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TL;DR: Multiple microsecond-length molecular dynamics simulations of complexes of Al(III) with amyloid-β (Aβ) peptides of varying length are reported, employing a non-bonded model of Al-coordination to the peptide, which is modelled using the AMBER ff14SB forcefield.
Abstract: Multiple microsecond-length molecular dynamics simulations of complexes of Al(III) with amyloid-β (Aβ) peptides of varying length are reported, employing a non-bonded model of Al-coordination to the peptide, which is modelled using the AMBER ff14SB forcefield. Individual simulations reach equilibrium within 100 to 400 ns, as determined by root mean square deviations, leading to between 2.1 and 2.7 μs of equilibrated data. These reveal a compact set of configurations, with radius of gyration similar to that of the metal free peptide but larger than complexes with Cu, Fe and Zn. Strong coordination through acidic residues Glu3, Asp7 and Glu11 is maintained throughout all trajectories, leading to average coordination numbers of approximately 4 to 5. Helical conformations predominate, particularly in the longer Al-Aβ40 and Al-Aβ42 peptides, while β-strand forms are rare. Binding of the small, highly charged Al(III) ion to acidic residues in the N-terminus strongly disrupts their ability to engage in salt bridges, whereas residues outside the metal binding region engage in salt bridges to similar extent to the metal-free peptide, including the Asp23-Lys28 bridge known to be important for formation of fibrils. High helical content and disruption of salt bridges leads to characteristic tertiary structure, as shown by heat maps of contact between residues as well as representative clusters of trajectories.
22 citations
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TL;DR: Molecular dynamics simulations of three possible adducts of Fe(II) to the N-terminal 1–16 fragments of the amyloid-β peptide are reported, along with analogous simulations of Cu (II) and Zn(II), indicating similarity of four-coordinate Cu and ZN complexes, compared to five-coordinated Fe complex that exhibits lower stability and weaker metal–ligand bonding.
Abstract: We report molecular dynamics simulations of three possible adducts of Fe(II) to the N-terminal 1-16 fragment of the amyloid-β peptide, along with analogous simulations of Cu(II) and Zn(II) adducts. We find that multiple simulations from different starting points reach pseudo-equilibration within 100 to 300 ns, leading to over 900 ns of equilibrated trajectory data for each system. The specifics of the coordination modes for Fe(II) have only a weak effect on peptide secondary and tertiary structure, and we therefore compare one of these with analogous models of Cu(II) and Zn(II) complexes. All share broadly similar structural features, with mixture of coil, turn and bend in the N-terminal region and helical structure for residues 11-16. Within this overall pattern, subtle effects due to changes in metal are evident: Fe(II) complexes are more compact, and are more likely to occupy bridge and ribbon regions of Ramachandran maps, while Cu(II) coordination leads to greater occupancy of the poly-proline region. Analysis of representative clusters in terms of molecular mechanics energy and Atoms-in-Molecules properties indicates similarity of 4-coordinate Cu and Zn complexes, compared to 5-coordinate Fe complex that exhibits lower stability and weaker metal-ligand bonding.
10 citations
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Helmholtz-Zentrum Dresden-Rossendorf1, Tokyo Institute of Technology2, University of Potsdam3, PSL Research University4, Karlsruhe Institute of Technology5, Lawrence Livermore National Laboratory6, Royal Institute of Technology7, Los Alamos National Laboratory8, Aix-Marseille University9, Technische Universität München10, Pacific Northwest National Laboratory11, Centre national de la recherche scientifique12, Institut de radioprotection et de sûreté nucléaire13, Dresden University of Technology14, Environmental Molecular Sciences Laboratory15, Cardiff University16, Heidelberg University17, Clemson University18, University of the South, Toulon-Var19, Université Paris-Saclay20, Agency for Science, Technology and Research21, European Synchrotron Radiation Facility22, University of Manitoba23, University of Paris-Sud24
TL;DR: The multimethodologic approach and the conclusions drawn address not only important aspects of actinide spectroscopy but particularly general aspects of modern molecular analytical chemistry.
Abstract: A comprehensive molecular analysis of a simple aqueous complexing system—U(VI) acetate—selected to be independently investigated by various spectroscopic (vibrational, luminescence, X-ray absorption, and nuclear magnetic resonance spectroscopy) and quantum chemical methods was achieved by an international round-robin test (RRT). Twenty laboratories from six different countries with a focus on actinide or geochemical research participated and contributed to this scientific endeavor. The outcomes of this RRT were considered on two levels of complexity: first, within each technical discipline, conformities as well as discrepancies of the results and their sources were evaluated. The raw data from the different experimental approaches were found to be generally consistent. In particular, for complex setups such as accelerator-based X-ray absorption spectroscopy, the agreement between the raw data was high. By contrast, luminescence spectroscopic data turned out to be strongly related to the chosen acquisition parameters. Second, the potentials and limitations of coupling various spectroscopic and theoretical approaches for the comprehensive study of actinide molecular complexes were assessed. Previous spectroscopic data from the literature were revised and the benchmark data on the U(VI) acetate system provided an unambiguous molecular interpretation based on the correlation of spectroscopic and theoretical results. The multimethodologic approach and the conclusions drawn address not only important aspects of actinide spectroscopy but particularly general aspects of modern molecular analytical chemistry.
6 citations
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TL;DR: A bimolecular photoinduced mechanism is proposed to account for the formation of mer-[Cr(CO)3(κ1-dppp)(κ2- dppp)]+ and trans-[Cr (CO)2(dppP)2]+.
6 citations
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TL;DR: In this article replica exchange molecular dynamics simulations of the complex formed between amyloid-β peptides and platinum bound to a phenanthroline ligand, Pt(phen), were performed.
Abstract: We report replica exchange molecular dynamics (REMD) simulations of the complex formed between amyloid-β peptides and platinum bound to a phenanthroline ligand, Pt(phen). After construction of an AMBER-style forcefield for the Pt complex, REMD simulation employing temperatures between 270 and 615 K was used to provide thorough sampling of the conformational freedom available to the peptide. We find that the full length peptide Aβ42, in particular, frequently adopts a compact conformation with a large proportion of α- and 3,10-helix content, with smaller amounts of β-strand in the C-terminal region of the peptide. Helical structures are more prevalent than in the metal-free peptide, while turn and strand conformations are markedly less common. Non-covalent interactions, including salt-bridges, hydrogen bonds, and π-stacking between aromatic residues and the phenanthroline ligand, are common, and markedly different from those seen in the amyloid-β peptides alone.
3 citations
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TL;DR: Vibrational and magnetism data support the oxidation state formulism of Cs4 in MeCN or DMF, and are corroborated by computational methodology.
Abstract: Oxidation of Cs4[U(NCS)8] in MeCN or DMF affords structurally characterised examples of the mixed-valent UIV/VI compound Cs14[{U(NCS)8}3{UO2(NCS)4(H2O)}]·4.5H2O, or the [UIV-UV-UIV][UVI] species [U(DMF)8(μ-O)U(NCS)5(μ-O)U(DMF)7(NCS)][UO2(NCS)5]. Vibrational and magnetism data support their oxidation state formulism, which is further corroborated by computational methodology.
1 citations