Yannick Coppel

Bio: Yannick Coppel is an academic researcher from University of Toulouse. The author has contributed to research in topics: Nanoparticle & Catalysis. The author has an hindex of 33, co-authored 149 publications receiving 3874 citations. Previous affiliations of Yannick Coppel include École Normale Supérieure & Centre national de la recherche scientifique.

Surface Chemistry of InP Quantum Dots: A Comprehensive Study

Abstract: Advanced 1H, 13C, and 31P 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 conditi...

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

Abstract: Iron has been implicated in Alzheimer's 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.

Structural and thermodynamical properties of CuII amyloid-β16/28 complexes associated with Alzheimer’s disease

Abstract: The aggregation of the peptide amyloid-β (Aβ) to form amyloid plaques is a key event in Alzheimer’s disease. It has been shown that CuII can bind to soluble Aβ and influence its aggregation properties. Three histidines and the N-terminal amine have been proposed to be involved in its coordination. Here, for the first time, we show isothermal titration calorimetry (ITC) measurements of the CuII binding to Aβ16 and Aβ28, models of the soluble Aβ. Moreover, different spectroscopic methods were applied. The studies revealed new insights into these CuII–Aβ complexes: (1) ITC showed two CuII binding sites, with an apparent Kd of 10−7 and 10−5 M, respectively; (2) the high-affinity site has a smaller enthalpic contribution but a larger entropic contribution than the low-affinity binding site; (3) azide did not bind to CuII in the higher-affinity binding site, suggesting the absence of a weak, labile ligand; (4) azide could bind to the CuII in the low-affinity binding site in Aβ28 but not in Aβ16; (5) 1H-NMR suggests that the carboxylate of aspartic acid in position 1 is involved in the ligation to CuII in the high-affinity binding site; (6) the pKa of 11.3 of tyrosine in position 10 was not influenced by the binding of 2 equivalents of CuII.

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

Abstract: 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

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

Abstract: 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.

Mechanism of oxidation reactions catalyzed by cytochrome p450 enzymes.

Abstract: ion phase that leads to an alkyl radical coordinated to the iron-hydroxo complex by a weak OH---C hydrogen bond, labeled as CI; (ii) an alkyl (or OH) rotation phase whereby the alkyl group achieves a favorable orientation for rebound; and (iii) a rebound phase that leads to C-O bond making and the ferric-alcohol complexes, 4,2P. The two profiles remain close in energy throughout the first two phases and then bifurcate. Whereas the HS state exhibits a significant barrier and a genuine TS for rebound, in the LS state, once the right orientation of the alkyl group is achieved, the LS rebound proceeds in a virtually barrier-free fashion to the alcohol. As such, alkane hydroxylation proceeds by TSR,70-72,120 in which the HS mechanism is truly stepwise with a finite lifetime for the radical intermediate, whereas the LS mechanism is effectively concerted with an ultrashort lifetime for the radical intermediate. Subsequent studies of ethane and camphor hydroxylation by the Yoshizawa group117,181-183 arrived at basically the same conclusion, that the mechanism is typified by TSR. The differences between the results of Shaik et al.130,173,177-180 and Yoshizawa et al.117,181-183 were rationalized recently71,72 and shown to arise owing to technical problems and the choice of the mercaptide ligand,117,181-183 which is a powerful electron donor and is too far from the representation of cysteine in the protein environment. The most recent study of camphor hydroxylation, which was done at a higher quality,117 converged to the picture reported by Shaik et al.130,173,177-180 and shows a stepwise HS process with a barrier of more than 3 kcal/mol for C-O bond formation by rebound of the camphoryl radical vis-à-vis an effectively concerted LS process for which this barrier is 0.7 kcal mol-1 and is the rotational barrier for reaching the rebound position. By referring to Figure 21, it is possible to rationalize the clock data of Newcomb in a simple manner. The apparent lifetimes are based on the assumption that there is a single state that leads to the reaction, such that the radical lifetime can be quantitated from the rate constant of free radical rearrangement and the ratio of rearranged to unrearranged alcohol product. However, in TSR, the rearranged (R) product is formed only/mainly on the HS surface, while the unrearranged (U) product is formed mainly on Figure 20. Formal descriptions of iron(III)-peroxo, iron(III)-hydroperoxo, and iron(V)-oxo species with indication of the negative charges. The roles “electrophile” or “nucleophile” are assigned according to the charge type. Reprinted with permission from ref 7. Copyright 2000 Springer-Verlag Heidelberg. 3964 Chemical Reviews, 2004, Vol. 104, No. 9 Meunier et al.

The re-emergence of natural products for drug discovery in the genomics era

Abstract: Natural products have been a rich source of compounds for drug discovery. However, their use has diminished in the past two decades, in part because of technical barriers to screening natural products in high-throughput assays against molecular targets. Here, we review strategies for natural product screening that harness the recent technical advances that have reduced these barriers. We also assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products, and highlight recent examples of natural products in antimicrobial drug discovery and as inhibitors of protein-protein interactions. The growing appreciation of functional assays and phenotypic screens may further contribute to a revival of interest in natural products for drug discovery.

Magnetically recoverable nanocatalysts.

Abstract: We gratefully acknowledge funding and support from King Abdullah University of Science and Technology (KAUST). Thanks are also due to the KAUST communication department for designing several images for this Review.

Highly Dynamic Ligand Binding and Light Absorption Coefficient of Cesium Lead Bromide Perovskite Nanocrystals

Abstract: Lead halide perovskite materials have attracted significant attention in the context of photovoltaics and other optoelectronic applications, and recently, research efforts have been directed to nanostructured lead halide perovskites. Collodial nanocrystals (NCs) of cesium lead halides (CsPbX3, X = Cl, Br, I) exhibit bright photoluminescence, with emission tunable over the entire visible spectral region. However, previous studies on CsPbX3 NCs did not address key aspects of their chemistry and photophysics such as surface chemistry and quantitative light absorption. Here, we elaborate on the synthesis of CsPbBr3 NCs and their surface chemistry. In addition, the intrinsic absorption coefficient was determined experimentally by combining elemental analysis with accurate optical absorption measurements. 1H solution nuclear magnetic resonance spectroscopy was used to characterize sample purity, elucidate the surface chemistry, and evaluate the influence of purification methods on the surface composition. We fi...

Oxidative stress and the amyloid beta peptide in Alzheimer's disease.

Abstract: Oxidative stress is known to play an important role in the pathogenesis of a number of diseases. In particular, it is linked to the etiology of Alzheimer's disease (AD), an age-related neurodegenerative disease and the most common cause of dementia in the elderly. Histopathological hallmarks of AD are intracellular neurofibrillary tangles and extracellular formation of senile plaques composed of the amyloid-beta peptide (Aβ) in aggregated form along with metal-ions such as copper, iron or zinc. Redox active metal ions, as for example copper, can catalyze the production of Reactive Oxygen Species (ROS) when bound to the amyloid-β (Aβ). The ROS thus produced, in particular the hydroxyl radical which is the most reactive one, may contribute to oxidative damage on both the Aβ peptide itself and on surrounding molecule (proteins, lipids, …). This review highlights the existing link between oxidative stress and AD, and the consequences towards the Aβ peptide and surrounding molecules in terms of oxidative damage. In addition, the implication of metal ions in AD, their interaction with the Aβ peptide and redox properties leading to ROS production are discussed, along with both in vitro and in vivo oxidation of the Aβ peptide, at the molecular level.