Yannick Coppel

Surface Chemistry of InP Quantum Dots: A Comprehensive Study

Advanced (1)H, (13)C, and (31)P solution and solid-state NMR studies combined with IR spectroscopy were used to probe, at the molecular scale, the composition and the surface chemistry of indium phosphide (InP) quantum dots (QDs) prepared via a non-coordinating solvent strategy. This nanomaterial can be described as a core-multishell object: an InP core, with a zinc blende bulk structure, is surrounded first by a partially oxidized surface shell, which is itself surrounded by an organic coating. This organic passivating layer is composed, in the first coordination sphere, of tightly bound palmitate ligands which display two different bonding modes. A second coordination sphere includes an unexpected dialkyl ketone and residual long-chain non-coordinating solvents (ODE and its isomers) which interact through weak intermolecular bonds with the alkyl chains of the carboxylate ligands. We show that this ketone is formed during the synthesis process via a decarboxylative coupling route and provides oxidative conditions which are responsible for the oxidation of the InP core surface. This phenomenon has a significant impact on the photoluminescence properties of the as-synthesized QDs and probably accounts for the failure of further growth of the InP core.

Deprotonation of the Asp1Ala2 Peptide Bond Induces Modification of the Dynamic Copper(II) Environment in the Amyloid‐β Peptide near Physiological pH

Aggregation of the amyloid-b (Ab) peptide and the production of reactive oxygen species by aggregates are two key features in Alzheimer’s disease. Copper ions have been linked to both of these events, 3] and hence determination of the basic interaction of Cu and Ab is essential for understanding its roles in the development of the pathology. The native Ab peptides consist of 39 to 43 amino acid residues and have been shown to be strongly prone to aggregation (from a few mm concentration). However, the Cu binding site has been localized in the N-terminal part of the peptide encompassing the first 16 amino acid residues (see Scheme S1 in the Supporting Information for the peptide sequence), 5] a truncated peptide that is highly soluble. Hence, this shortened peptide is accepted as a valuable model of Cu coordination to full-length Ab and its high solubility allows classical spectroscopic methods, such as those of the present study, to be used. While most techniques aim at identifying the Cu ligands (for a review, see reference [6] and for very recent reports, see references [7, 8]), NMR spectroscopy is among the few methods also able to reveal dynamical processes in the coordination of Cu to Ab. Indeed, the paramagnetism of the Cu ion induces an enhancement of the relaxation rate of the peptide nuclei, this effect diminishing according to the inverse sixth power of the interatomic distance (for reviews, see references [9, 10]). Consequently, selective broadening of the NMR signals of nuclei spatially close to the metal-ion binding site(s) is observed. In the case of Cu, the line broadening is severe and the effect of the largely substoichiometric ratio of the paramagnetic ion is detectable in the case of fast exchange of the paramagnet between sites. This is also true for C NMR signals despite the lower sensitivity to broadening effects for this nucleus as a result of its lower gyromagnetic ratio compared to that of the proton. As concerns Cu coordination to Ab, only a few NMR studies have been reported and they are limited to H NMR or H–N heteronuclear single quantum correlation (HSQC) experiments. 14] Fast amide proton exchanges are responsible for the loss of the signals of several amino acids (including Asp1 and the three His residues) in apo–Ab peptide in the latter cases, an effect that precludes the analysis of Cu-induced signal broadening. For those reasons, herein we focus on C{H} NMR spectroscopy, which is a straightforward way to inspect the effect of Cu on Ab peptide signals. Furthermore, it is known that near physiological pH, two Cu complexes of Ab coexist, which differ in the protonation state of the peptide and their spectroscopic signatures. 15] They are referred to below as “low-pH” and “high-pH” species. We identify the amino acid residues involved in Cu binding, and give clear-cut evidence for the presence of equilibria between different ligands in both forms. We also give new insights into the dramatic change undergone by the Cu binding sites in Ab between pH values of about 6.6 and 8.7, which arises from the deprotonation and binding of the Asp1 Ala2 peptide bond amide. Figure 1 shows the evolution of the C{H} NMR spectra of the Ab peptide (sequence DAEFRHDSGYEVHHQK) upon addition of 0.1 equivalents of Cu at pH 6.6 and 8.7 (see also Figure S4 in the Supporting Information for spectral domains that concern His residues). 17] Addition of Cu leads to broadening of several signals that is more selective at high pH (right-hand spectra in Figure 1) with only Asp1, Ala2, and the side chain of His mainly affected. More precisely, at pH 6.6 peaks of the carboxylate groups from Asp1, Asp7, Glu3, Glu11, and the unprotected C terminus are significantly broadened with a slight preference for that of Asp7. Only that of Asp1 is broadened at pH 8.7. Peaks of the [*] Dr. C. Hureau, Dr. Y. Coppel, Dr. L. Sabater, Prof. Dr. P. Faller CNRS; LCC (Laboratoire de Chimie de Coordination) 205 route de Narbonne, 31077 Toulouse (France) and Universit de Toulouse; UPS, INPT; LCC 31077 Toulouse (France) Fax: (+ 33)5-6155-3003 E-mail: christelle.hureau@lcc-toulouse.fr peter.faller@lcc-toulouse.fr

Iron(II) binding to amyloid-β, the Alzheimer's peptide.

Iron has been implicated in Alzheimers disease, but until now no direct proof of Fe(II) binding to the amyloid-β peptide (Aβ) has been reported. We used NMR to evidence Fe(II) coordination to full-length Aβ40 and truncated Aβ16 peptides at physiological pH and to show that the Fe(II) binding site is located in the first 16 amino-acid residues. Fe(II) caused selective broadening of some NMR peaks that was dependent on the Fe:Aβ stoichiometry and temperature. Analysis of Fe(II) broadening effect in the (1)H, (13)C, and 2D NMR data established that Asp1, Glu3, the three His, but not Tyr10 nor Met35 are the residues mainly involved in Fe(II) coordination.

Tailored Control and Optimisation of the Number of Phosphonic Acid Termini on Phosphorus‐Containing Dendrimers for the Ex‐Vivo Activation of Human Monocytes

The syntheses of a series of phosphonic acid-capped dendrimers is described. This collection is based on a unique set of dendritic structural parameters-cyclo(triphosphazene) core, benzylhydrazone branches and phosphonic acid surface-and was designed to study the influence of phosphonate (phosphonic acid) surface loading towards the activation of human monocytes ex vivo. Starting from the versatile hexachloro-cyclo(triphosphazene) N(3)P(3)Cl(6), six first-generation dendrimers were obtained, bearing one to six full branches, that lead to 4, 8, 12, 16, 20 and 24 phosphonate termini, respectively. The surface loading was also explored at the limit of dense packing by means of a first-generation dendrimer having a cyclo(tetraphosphazene) core and bearing 32 termini, and with a first-generation dendrimer based on a AB(2)/CD(5) growing pattern and bearing 60 termini. Human monocyte activation by these dendrimers confirms the requirement of the whole dendritic structure for bioactivity and identifies the dendrimer bearing four branches, thus 16 phosphonate termini, as the most bioactive.

Importance of dynamical processes in the coordination chemistry and redox conversion of copper amyloid-β complexes

Interaction of Cu ions with the amyloid-β (Aβ) peptide is linked to the development of Alzheimer’s disease; hence, determining the coordination of CuI and CuII ions to Aβ and the pathway of the CuI(Aβ)/CuII(Aβ) redox conversion is of great interest. In the present report, we use the room temperature X-ray absorption near edge structure to show that the binding sites of the CuI and CuII complexes are similar to those previously determined from frozen-solution studies. More precisely, the CuI is coordinated by the imidazole groups of two histidine residues in a linear fashion. However, an NMR study unravels the involvement of all three histidine residues in the CuI binding due to dynamical exchange between several set of ligands. The presence of an equilibrium is also responsible for the complex redox process observed by cyclic voltammetry and evidenced by a concentration-dependent electrochemical response.

Characterization of the ZnII binding to the peptide amyloid-β1-16 linked to Alzheimer's disease

Aggregation of the human peptide amyloid‐β (Aβ) is a key event in Alzheimers disease (AD). Zinc ions play an important role in AD and in Aβ aggregation. In vitro, ZnII binds to Aβ and accelerates its aggregation. In this work we have investigated ZnII binding to the synthetic peptide Aβ1–16, which contains the metal‐binding domain of Aβ. CdII was used to probe the ZnII site. Aβ1–16 bound one equivalent of ZnII with an apparent dissociation constant (Kd) of 10−4 M. This Kd value is in the same range as the Zn concentration needed to precipitate Aβ. Circular dichroism and NMR indicated predominantly random‐coil secondary structures of apo‐Aβ1–16, ZnII–Aβ1–16 and CdII–Aβ1–16, which were all highly dynamic and flexible. The three histidines at positions 6, 13 and 14 were suggested to be ligands to ZnII and CdII. Evidence that the aspartate at position 1 served as a fourth ligand to ZnII and CdII was found at pH 8.7. 111CdII NMR showed a resonance at 84 ppm, in line with a mixed oxygen‐/nitrogen‐ligand environment. The tyrosine at position 10 could be excluded as a ligand.

Gold(I) Complexes of Phosphanyl Gallanes: From Interconverting to Separable Coordination Isomers†

Gallant exchange: Upon coordination of phosphanyl gallane ligands to AuCl, both neutral and zwitterionic complexes coexist. NMR spectroscopy provides direct evidence for the transfer of the chloride between gold and gallium in diphosphanyl gallane. The introduction of a third phosphanyl buttress allows the separation and structural characterization of the two coordination isomers (see picture; Au yellow, P red, Cl green, Ga blue).

Amyloid-Beta Peptide Forms Monomeric Complexes With CuII and ZnII Prior to Aggregation

The aggregation of the peptide amyloid-b (Ab) into fibrils is considered to be a key event in Alzheimer’s disease. In vivo, the most prevalent forms of Ab consist of 40 (Ab40) or 42 amino acids (Ab42). Neuronal dysfunction has been proposed to be mediated predominantly by aggregation intermediates rather than fully formed fibrils of these peptides; however, both fibrils and smaller oligomers have been found to be neurotoxic. Several intermediates have been described, ranging in size from dimers up to large aggregates (diameter of ~10 nm). The conditions that influence aggregation and the formation of intermediates are of great interest, and, here, an important role for Zn and Cu has been shown. Elevated concentrations of Zn and Cu have been found in amyloid plaques. These metal ions bind at the N-terminal (amino acids 1–16) and influence aggregation behavior. Whereas Zn accelerates aggregation, for Cu, slowing down and acceleration of aggregation have been reported, probably due to the different conditions used. Under our conditions (see the Supporting Information), the following order, from the highest to the least aggregated, has been measured: [Zn–Ab40]> [Cu2–Ab40]> [apo-Ab40] [Cu1–Ab40]> [apo-Ab40, in the presence of the metal chelator deferoxamine]. Metal-induced aggregation of a peptide/protein can be conceptually divided into two mechanisms: 1) the metal binds to ligands originating from two molecules of Ab and forms a bridge (Scheme 1A); 2) the metal binds to Ab as a monomeric complex and induces a conformational change that favors aggregation by pure peptide–peptide contacts (Scheme 1B). Intermediate mechanisms are also possible, such as formation of metal-induced dimers (Scheme 1C), which then aggregate by binding to other dimers by peptide–peptide contacts. Here we addressed the question of whether metal binding to Ab induces dimerization. Such a metal-induced dimer would be of importance because:

Full Characterization of Colloidal Solutions of Long‐Alkyl‐Chain‐Amine‐Stabilized ZnO Nanoparticles by NMR Spectroscopy: Surface State, Equilibria, and Affinity

Full NMR characterization of ZnO nanoparticles (NPs) stabilized by various amines (hexadecylamine, dodecylamine, and octylamine) in C(7)D(8) demonstrated that the surface of this apparently simple system was very complex. Using different NMR spectroscopic techniques ((1)H, PGSE-NMR, diffusion-filtered (1)H NMR, NOESY, ROESY), we observed at least three different modes of interaction of the amines at the surface of the NPs, in thermodynamic equilibrium with the free amines, the relative populations of which varied with their concentration. The first mode corresponded to a strong interaction between a small amount of amine and the ZnO NPs (k(desorp)≈13 s(-1)). The second mode corresponded to a weak interaction between the amines and the surface of the ZnO NPs (k(off(2))≈50-60 s(-1)). The third, and weakest, mode of interaction corresponded to the formation of a second ligand shell by the amine around the NPs that was held together through van der Waals interactions (k(off(1))≈25×10(5) s(-1)). The second and third modes were in fast exchange on the NMR timescales with the free amines. The strongly interacting amines at the NPs surface (first mode) were in slow exchange with the other modes. A complex hydrogen-bonding network at the NPs surface was also observed, which did not only involve the coordinated amine but also THF and water molecules that remained from the synthesis.

Hypervalent Silicon Compounds by Coordination of Diphosphine–Silanes to Gold

Coordination of ambiphilic diphosphine-silane ligands [o-(iPr(2)P)C(6)H(4)](2)Si(R)F (R=F, Ph, Me) to AuCl affords pentacoordinate neutral silicon compounds in which the metal atom acts as a Lewis base. X-ray diffraction analyses, NMR spectroscopy, and DFT calculations substantiate the presence of Au→Si interactions in these complexes, which result in trigonal-bipyramidal geometries around silicon. The presence of a single electron-withdrawing fluorine atom is sufficient to observe coordination of the silane as a σ-acceptor ligand, provided it is positioned trans to gold. The nature of the second substituent at silicon (R=F, Ph, Me) has very little influence on the magnitude of the Au→Si interaction, in marked contrast to N→Si adducts. According to variable-temperature and 2D EXSY NMR experiments, the apical/equatorial positions around silicon exchange in the slow regime of the NMR timescale. The two forms, with the fluorine atom in trans or cis position to gold, were characterized spectroscopically and the activation barrier for their interconversion was estimated. The bonding and relative stability of the two isomeric structures were assessed by DFT calculations.