The necessity of having a tetradentate ligand to extract copper(II) ions from amyloids

International audienceThe accumulation of redox-active metal ions, in particular copper, in amyloid plaques is considered to the cause of the intensive oxidation damage to the brain of patients with Alzheimers disease (AD). Drug candidates based on a bis(8-aminoquinoline) tetradentate ligand are able to efficiently extract Cu2+ from copper-loaded amyloids (Cu–Aβ). Contrarily, in the presence of a bidentate hydroxyquinoline, such as clioquinol, the copper is not released from Aβ, but remains sequestrated within a Aβ–Cu–clioquinol ternary complex that has been characterized by mass spectrometry. Facile extraction of copper(II) at a low amyloid/ligand ratio is essential for the re-introduction of copper in regular metal circulation in the brain. As, upon reduction, the Cu+ is easily released from the bis(8-aminoquinoline) ligand unable to accommodate CuI, it should be taken by proteins with an affinity for copper. So, the tetradentate bis(8-aminoquinoline) described here might act as a regulator of copper homeostasis

Micro- and nanocrystals of the iron(iii) spin-transition material [FeIII(3-MeO-SalEen)2]PF6

International audienceThe elaboration of micro-and nanometric particles of [Fe III (3-MeO-SalEen)2]PF6 (H-3-MeO-SalEen being the condensation product of 3-methoxy-substituted salicylaldehyde and N-ethylethylenediamine), a spin-transition compound of molecular nature, is reported. A sudden precipitation approach, using butan-1-ol as an anti-solvent, has been shown to produce crystalline objects, whose size and shape can be modulated by varying the selected experimental parameters (temperature, solvent, polymeric confining agent). They are in the form of either needle-shaped (7500x640x215 (a); 3500x350x125 (b); 950x270 x35 nm 3 (c)) or spherical particles (18 ± 3 nm (d)). The chemical nature of these molecular materials has been confirmed by EDS and Raman spectroscopies. The RT powder X-ray diffractograms indicate the formation of size-reduced particles (a-d) of crystalline character, which correspond to the unperturbed phase previously reported by Hendrickson and coworkers. Magnetic, EPR and Raman investigations demonstrate the occurrence of a low-spin high-spin transition. In agreement with literature, disappearence of the weak hysteresis and decrease of cooperative character indicate weaker interactions within size-reduced particles. Two striking features: (i) the small shift in the transition temperatures from 162 K (bulk) to 153 K (18 nm) and (ii) the very quantitative spin transformation (fraction of HS residues 5%) contrast to those usually reported for coordination networks and point towards specificity of molecular nanomaterials

C–O and C–N Functionalization of Cationic, NCN-Type Pincer Complexes of Trivalent Nickel: Mechanism, Selectivity, and Kinetic Isotope Effect

International audienceThis report presents the synthesis of new mono- and dicationic NCN-NiIII complexes and describes their reactivities with protic substrates. (NCN is the pincer-type ligand κN, κC, κN-2,6-(CH2NMe2)2-C6H3.) Treating van Koten’s trivalent complex (NCN)NiIIIBr2 with AgSbF6 in acetonitrile gives the dicationic complex [(NCN)NiIII(MeCN)3]2+, whereas the latter complex undergoes a ligand-exchange reaction with (NCN)NiIIIBr2 to furnish the related monocationic complex [(NCN)NiIII(Br)(MeCN)]+. These trivalent complexes have been characterized by X-ray diffraction analysis and EPR spectroscopy. Treating these trivalent complexes with methanol and methylamine led, respectively, to C-OCH3 or C-NH(CH3) functionalization of the Ni-aryl moiety in these complexes, C-heteroatom bond formation taking place at the ipso-C. These reactions also generate the cationic divalent complex [(NCN)NiII(NCMe)]+, which was prepared independently and characterized fully. The unanticipated formation of the latter divalent species suggested a comproportionation side reaction between the cationic trivalent precursors and a monovalent species generated at the C–O and C–N bond formation steps; this scenario was supported by direct reaction of the trivalent complexes with the monovalent compound (PPh3)3NiICl. Kinetic measurements and density functional theory analysis have been used to investigate the mechanism of these C–O and C–N functionalization reactions and to rationalize the observed inverse kinetic isotope effect in the reaction of [(NCN)NiIII(Br)(MeCN)]+ with CH3OH/CD3OD

Solution and single crystal spectroscopic characterization of (PPh4)2[Fe(CN)5(imidazole)]∙2H2O

The compound (PPh4)2[FeIII(CN)5(im)]∙2H2O (1) together with its 13C labeled analogue have been synthesized (where im is imidazole) and characterized by UV/Vis, LD, IR, Raman and resonance Raman spectroscopy both in solution, powder and single crystalline form. The low spin state of the metal center, FeIII, was confirmed by MCD, EPR and 57Fe Mössbauer spectroscopies. Polarized Raman spectroscopic studies on a single crystal of 1 show the strong dependence of the stretching cyano ligand vibrations on crystal orientation relative to the direction of laser polarization and allows for assignment of all CN vibrational modes. Raman, UV/Vis absorption, LD and MCD spectroscopy both in the solid state and in solution state allowed for the discrimination of the effect of protonation of the imidazole ligand and hydrogen bonding to the cyano ligands on the complex. The combined spectroscopic data demonstrates that in addition to the protonation state of the imidazole, hydrogen bonding interactions with the cyano ligands both in the solid state as well as in solution have a profound influence on the electronic properties of 1.

Two-step spin crossover phenomenon under high pressure in the coordination polymer Fe(3-methylpyridine)2[Ni(CN)4]

International audienceThe temperature dependence of the magnetic susceptibility and Mössbauer spectra of the compounds FeL2[Ni(CN)4] (L = 2, 3 or 4-methylpyridine) have been investigated. In each case the iron(II) ions are high spin at room temperature, but in the 3-methylpyridine compound about half of the iron ions becomes diamagnetic around 90 K. The application of external pressure allowed to uncover the underlying two-step nature of this spin transition. For further increase of the pressure the plateau between the two steps disappeared. Both observations were successfully interpreted in the framework of an Ising-like model with two iron sites displaying different volume changes

Nanocrystals of Fe(phen)(2)(NCS)(2) and the size-dependent spin-crossover characteristics

International audienceWe report on the size reduction of the neutral Fe(phen)(2)(NCS)(2) prototypical compound exhibiting a cooperative spin-crossover associated with a first-order phase transition (at ca. 176 K). We use the [Fe(phen)(3)](NCS)(2) ionic precursor and the solvent-assisted precipitation technique to prepare an array of crystalline objects with sizes varying over two orders of magnitude (from 15 up to 1400 nm). TEM, X-ray diffraction and IR measurements provide evidences for the formation of particles of neutral and ionic species, which results from the interplay between the relevant chemical equilibrium and the reaction kinetics (ligand extraction, complex precipitation), and the modulation of the latter by physico-chemical parameters. A thermal transformation of diamagnetic nanocrystals of [Fe(phen)(3)](NCS)(2) leads to spin-crossover particles of Fe(phen)(2)(NCS)(2) of a comparable size. Powders of nano-, micro-and polycrystals of Fe (phen)(2)(NCS)(2) present X-ray diffractograms typical of the so-called polymorph II. The importance of size effects on the cooperative spin-crossover process was probed with magnetic, Mossbauer, Raman and IR spectroscopic measurements. Each sample exhibits spin-state switching of the Fe(II) ions. The salient features are: a cooperativity preserved at the micrometric scale, a very limited downshift of the transition temperature and an asymmetric spreading of the thermal process (over ca. 100 K) with the size reduction. At temperatures close to room temperature, the process appears to be quasi complete whatever the size of the samples. This result, extracted from Raman data, was confirmed by Mssbauer measurements in the case of the largest objects (LS residue <5-10% for bulk and microparticles). Below 150 K, a very efficient low-spin to high-spin photoexcitation was induced by the Raman laser beam in all the samples which prevents the extraction of the high-spin fraction in this temperature range. However variable temperature IR spectra of the 29 nm particles indicate that the HS residue, that is close to zero in the case of microparticles, does not drastically increase (<30%) for the smallest particles. The processing of a number of related spin-crossover compounds in the form of nanoparticles may be achieved with this general approach

Photo- and thermo-induced spin crossover in a cyanide-bridged {Mo(V)2Fe(II)2} rhombus molecule

1364-548XInternational audienceThe self-assembly of [Mo(V)(CN)8](3-) and [Fe(II)(bik)2(S)2](2+) affords a cyanide-bridged {Mo(V)2Fe(II)2} rhombus molecule that shows photomagnetic effect under laser light irradiation at low temperature and exhibits thermo-induced spin crossover near ambient temperature

Fe(Me-2-bpy)(2)(NCSe)(2) spin-crossover micro- and nanoparticles showing spin-state switching above 250 K

International audienceWe present the study of nano- and microparticles of the Fe(Me-2-bpy)(2)(NCSe)(2) spin-crossover complex prepared from the diamagnetic precursor [Fe(Me-2-bpy)(3)](NCSe)(2)center dot S. Two solvates of the latter were characterized by single-crystal X-ray structures at 100 K (S = 2MeOH or 3H(2)O). The extraction of one Me-2-bpy per metal ion in [Fe(Me-2-bpy)(3)](NCSe)(2)center dot S was achieved either by thermolysis at temperature higher than 150 degrees C or by precipitation in an anti-solvent, leading to a polycrystalline or particulate powder of Fe(Me-2-bpy)(2)(NCSe)(2). This chemical conversion was investigated by TGA, powder X-ray diffraction, IR, Raman and magnetic measurements. The S = 0 S = 2 spin-crossover of Fe(Me-2-bpy)(2)-(NCSe)(2) centered at ca. 340 K is almost complete at low temperature (HS residue <= 5% below 250 K) while at 370 K, the HS fraction can be estimated at similar to 0.7. These features are essentially preserved whatever be the size of particles (56, 460 and 1200 nm) as a consequence of the weak cooperativity of the process occurring at high temperature, the crystallinity and the molecular nature of particles. This approach leading to dispersion of small particles in a polymer is suitable for the preparation of materials of optical quality, via the stabilization and processing of nanoparticles in convenient matrices to form thin films

Mechanistic insights into the in vitro metal-promoted oxidation of (di)azine hydroxamic acids: evidence of HNO release and N , O -di(di)azinoyl hydroxylamine intermediate

The oxidant-dependent ability of hydroxamic acids to release nitroxyl (HNO), a small inorganic molecule endowed with various biological properties, is addressed from a mechanistic standpoint. Indeed, the exact mechanism of the hydroxamic acid oxidation in physiological conditions and the direct or indirect characterization of the intermediates remain elusive. In this work, intermolecular oxidation of isonicotino-, nicotino- and pyrazino-hydroxamic acids with K3[FeIII(CN)6] at physiological pH (7.4), was monitored by 1H NMR, MS, EPR and UV-vis techniques. While nitrosocarbonyl (di)azine intermediates, (di)Az-C(O)-NO, could be a priori envisaged, it was in fact the corresponding N,O-di(di)azinoylhydroxylamines (AzC(O)NHOC(O)Az) and HNO that were identified, the first by 1H NMR and the second on the basis of EPR and UV-vis experiments using the [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide] (cPTIO) spin trap. The decomposition of the unstable N,O-di(di)azinoylhydroxylamine intermediates in aqueous buffer media was shown to generate the corresponding carboxylic acids as final organic products, envisaged as possible in vivo metabolites. The same oxidation experiments performed in the presence of methylamine led to the corresponding N-methyl amides suggesting that, unlike hydroxamic acids, N,O-di(di)azinoylhydroxylamines act as acylating agents in physiological pH conditions

pH-Dependent Cu(II) Coordination to Amyloid-β Peptide: Impact of Sequence Alterations, Including the H6R and D7N Familial Mutations.

Copper ions have been proposed to intervene in deleterious processes linked to the development of Alzheimer’s disease (AD). As a direct consequence, delineating how Cu(II) can be bound to amyloid-β (Aβ) peptide, the amyloidogenic peptide encountered in AD, is of paramount importance. Two different forms of [Cu^II(Aβ)] complexes are present near physiological pH, usually noted components <b>I</b> and <b>II</b>, the nature of which is still widely debated in the literature, especially for <b>II</b>. In the present report, the phenomenological pH-dependent study of Cu(II) coordination to Aβ and to ten mutants by EPR, CD, and NMR techniques is described. Although only indirect insights can be obtained from the study of Cu(II) binding to mutated peptides, they reveal very useful for better defining Cu(II) coordination sites in the native Aβ peptide. Four components were identified between pH 6 and 12, namely, components <b>I</b>, <b>II</b>, <b>III</b> and <b>IV</b>, in which the predominant Cu(II) equatorial sites are {−NH₂, CO (Asp1–Ala2), N_im (His6), N_im (His13 or His14)}, {−NH₂, N^– (Asp1–Ala2), CO (Ala2–Glu3), N_im}, {−NH₂, N^– (Asp1–Ala2), N^– (Ala2–Glu3), N_im} and {−NH₂, N^– (Asp1–Ala2), N^– (Ala2–Glu3), N^– (Glu3–Phe4)}, respectively, in line with classical pH-induced deprotonation of the peptide backbone encountered in Cu(II) peptidic complexes formation. The structure proposed for component <b>II</b> is discussed with respect to another coordination model reported in the literature, that is, {CO (Ala2–Glu3), 3 N_im}. Cu(II) binding to the H6R-Aβ and D7N-Aβ peptides, where the familial H6R and D7N mutations have been linked to early onset of AD, has also been investigated. In case of the H6R mutation, some different structural features (compared to those encountered in the native [Cu^II(Aβ)] species) have been evidenced and are anticipated to be important for the aggregating properties of the H6R-Aβ peptide in presence of Cu(II)