Novel 1-hydroxypyridin-2-one metal chelators prevent and res-cue ubiquitin proteasomal-related neuronal injury in an in vitro model of Parkinson’s disease

Ubiquitin proteasome system (UPS) impairment, excessive cellular oxidative stress and iron dyshomeostasis are key to substantia nigra dopaminergic neuronal de-generation in Parkinson's disease (PD); however, a link between these features remains unconfirmed. By using the proteasome inhibitor lactacystin we confirm that nigral injury via UPS impairment disrupts iron homeostasis, in turn increasing oxi-dative stress and promoting protein aggregation. We demonstrate the neuroprotec-tive potential of two novel 1-hydroxy-2(1H)-pyridinone (1,2-HOPO) iron chelators, compounds C6 and C9, against lactacystin-induced cell death. We demonstrate that this cellular preservation relates to the compounds’ iron chelating capabilities and subsequent reduced capacity of iron to form reactive oxygen species (ROS), where we also show that the ligands act as antioxidant agents. Our results also de-monstrate the ability of C6 and C9 to reduce intracellular lactacystin-induced α-synuclein burden. Stability constant measurements confirmed a high affinity of C6 and C9 for Fe3+ and display a 3:1 HOPO:Fe3+ complex formation at physiological pH. Reducing iron reactivity could prevent the demise of nigral dopaminergic neurons. We provide evidence that the lactacystin model presents with several neuropatho-logical hallmarks of PD related to iron dyshomeostasis and that the novel chelating compounds C6 and C9 can protect against lactacystin-related neurotoxicity

Complexation of lanthanides, actinides and transition metal cations with a 6-(1,2,4-triazin-3-yl)-2,2’:6’,2’’-terpyridine ligand: implications for actinide(III) /lanthanide(III) partitioning

The quadridentate N-heterocyclic ligand 6-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)-2,2’:6’,2’’-terpyridine (CyMe4-hemi-BTBP) has been synthesized and its interactions with Am(III), U(VI), Ln(III) and some transition metal cations have been evaluated by X-ray crystallographic analysis, Am(III)/Eu(III) solvent extraction experiments, UV absorption spectrophotometry, NMR studies and ESI-MS. Structures of the 1:1 complexes with Eu(III), Ce(III) and the linear uranyl (UO22+) ion were obtained by X-ray crystallographic analysis, and showed similar coordination behavior to related BTBP complexes. In methanol, the stability constants of the Ln(III) complexes are slightly lower than those of the analogous quadridentate bis-triazine BTBP ligands, while the stability constant for the Yb(III) complex is higher. 1H NMR titrations and ESI-MS with lanthanide nitrates showed that the ligand forms only 1:1 complexes with Eu(III), Ce(III) and Yb(III), while both 1:1 and 1:2 complexes were formed with La(III) and Y(III) in acetonitrile. A mixture of isomeric chiral 2:2 helical complexes was formed with Cu(I), with a slight preference (1.4:1) for a single directional isomer. In contrast, a 1:1 complex was observed with the larger Ag(I) ion. The ligand was unable to extract Am(III) or Eu(III) from nitric acid solutions into 1-octanol, except in the presence of a synergist at low acidity. The results show that the presence of two outer 1,2,4-triazine rings is required for the efficient extraction and separation of An(III) from Ln(III) by quadridentate N-donor ligand

Synthèse et étude des propriétés complexantes de dérivés amides et hydroxamiques des calix[4]arènes et de leurs analogues thiocarbonylés

Afin de pouvoir suivre les teneurs en cations de métaux lourds toxiques pour les organismes vivants tels que Pb2+ ou Cd2+, il est nécessaire de concevoir des composés hautement sélectifs. Ce travail porte sur la synthèse et l étude de dérivés amides et hydroxyamides de calix[4]arènes et de leurs analogues thiocarbonylés. Vingt sept dérivés (thioamides, amides, hydroxamates et acides hydroxamiques) ont été obtenus. Différentes techniques ont permis l étude des interactions entre ces ligands et des cations métalliques: spectroscopie RMN du 1H, diffraction des rayons X, extraction liquid-liquid, spectrophotométrie d absorption dans l UV, potentiométrie et microcalorimétrie. Le remplacement des atomes d oxygène des amides tertiaires par des atomes de soufre conduit à des composés très sélectifs pour Ag+ et Pb2+ par rapport aux cations des groupes I et II. Les dérivés acides hydroxamiques extraient très efficacement Fe3+ et Cu2+. Des résultats intéressants ont été obtenus avec ces composés permettant d envisager l'élimination et la séparation de Pb2+ d'autres métaux toxiques comme Cd2+. De plus, l utilisation de ces ligands pourrait permettre de séparer Cu2+ de Zn2+ et Ni2+ qui sont souvent présents simultanément. Les dérivés thioamides et hydroxamates ont été utilisés comme éléments sensibles dans la membrane d électrodes sélectives (ISEs). Les électrodes basées sur des dérivés thioamides, en particulier sur les composés porteurs de fonctions piperidinyles et morpholinyles devraient permettre le développement d outils analytiques prometteurs pour le contrôle des niveaux de pollution en Pb2+ dans les eaux naturelles et les eaux potables.The need of monitoring and controlling the concentration of heavy metal ions such as Pb2+ or Cd2+, which have toxic effects on all living organisms inspires chemists to synthesise more and more selective compounds. The aim of this work was the synthesis of amide and hydroxyamide derivatives of calix[4]arenes and their thiocarbonyl analogues. Nine thioamide derivatives as well as their respective amide derivatives, five hydroxamate derivatives and four calix[4]arene-hydroxamic acids were obtained. Studies of ligands interaction with metal cations were investigated using different techniques: 1H NMR spectroscopy, X-ray diffraction, liquid-liquid extraction, UV absorption spectrophotometry, potentiometry and microcalorimetry. The replacement of the oxygen atoms by sulphur atoms in the tertiary amide structures led to compounds highly selective for Ag+ and Pb2+ over I and II group of cations. Hydroxamic acids of calix[4]arene occurred to be efficient extractants for Fe3+ and Cu2+. Moreover, very important results obtained with these compounds could find an application in the context of the removal and separation of Pb2+ from other toxic metals such as Cd2+. In addition, these ligands could be used to separate Cu2+ from Ni2+ and Zn2+, which are often found together. Selectivity of thioamide and hydroxamate derivatives was assessed using these ligands as sensor materials in ion-selective membrane electrodes. Electrodes based on calix[4]arene-thioamides, particularly on compounds bearing piperidinyl and morpholinyl substituents are promising analytical tools for monitoring Pb2+ concentration in natural and drinking waters.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Valorisation de mâchefers d’incinération d’ordures ménagèresPartie 2 : étude sur le terrain (chaussées) et en laboratoires (lysimètres)

Bottom ash (BA) is the main residue obtained after incineration of municipal solid wastes. In France, its production rises 2.7 million tons annually. Utilization of BA in road works and embankments is encouraged in France but strictly regulated. In order to evaluate the environmental impact of BA used in road construction under real conditions, two road sections were studied. Nevertheless, this study requires technical and financial means which are important. In this context, a laboratory tool (lysimeter) has been developed in which it is possible to reproduce the conditions of utilization. The experiments carried out during three years, have shown a low contribution of BA on the composition of the percolation water and a low toxicity has been measured on percolates at the end of the study. The different tests carried out in lysimeters have shown a good reproducibility of the composition of the percolate. The correlation between the lysimeters and the road sections has not been clearly observed.Les mâchefers sont les principaux résidus (en poids) de l’incinération des ordures ménagères. Leur production, en France, s’élève à 2,7 millions de tonnes par an. Compte tenu de la nécessité de maîtriser leur utilisation en technique routière, il est intéressant d’étudier cette valorisation en milieu réel par le suivi de chaussées expérimentales. Il s’agit cependant d’une démarche lourde et onéreuse, d’où la mise au point en complément d’un outil de laboratoire (lysimètre) permettant de simuler différentes conditions de valorisation. La valorisation en conditions réelles d’un mâchefer a été étudiée grâce au suivi de deux chaussées expérimentales sur une durée de 3 ans. D’une manière générale, un faible apport des mâchefers a été mesuré sur la composition des eaux de percolation. Une faible toxicité des percolats a été observée en fin de suivi. Les différents essais effectués en lysimètres ont permis de montrer une bonne reproductibilité de la composition des percolats. La corrélation avec les chaussées n’a pas encore pu être clairement établie

Valorisation de mâchefers d’incinération d’ordures ménagèresPartie 1 : caractérisation des mâchefers

France incinerates about 40% of its municipal solid waste (MSW), producing 2.7 million tons of bottom ash annually. Utilization of bottom ash is encouraged in France but strictly regulated. Only bottom ash meeting specific criteria and produced in accordance with a quality assurance plan can be used in road works. It is then important to study their characteristics before its utilization in real conditions. Geotechnic characteristics and low leachable fraction obtained on a studied bottom ash are in accordance with the regulation to be used in road construction. The study of its composition has shown the presence of major elements (Si, Ca, Al, S), minor elements (Cr, Mn, Cu, Pb, Ni, Zn) and trace elements (As, Cd, Hg, Se) which have been quantified.En France, environ 40 % des ordures ménagères sont incinérées produisant 2,7millions de tonnes de mâchefers par an. Il est possible d’utiliser ce déchet en technique routière s’il répond à des critères bien spécifiques (circulaire ministérielle du 9 mai 1994). Il est donc important de connaître les caractéristiques des mâchefers avant de rendre effective leur valorisation. L’objet de ce travail est d’abord de caractériser un mâchefer d’incinération d’ordures ménagères destiné à être valorisé. Les caractéristiques géotechniques et la faible fraction lixiviable déterminées sur ce mâchefer permettent, selon la réglementation, son utilisation en technique routière. Par ailleurs, la détermination de sa composition élémentaire a montré la présence d’éléments majeurs (Si, Ca, Al, S), mineurs (Cr, Mn, Cu, Pb, Ni, Zn) et traces (As, Cd, Hg, Se) dont les différentes teneurs ont été quantifiées

Competitive adsorption mechanisms of Cd(<scp>ii</scp>), Cu(<scp>ii</scp>) and Pb(<scp>ii</scp>) on bioinspired mesoporous silica revealed by complementary adsorption/isothermal titration calorimetry studies

International audienceThis work presents an original adsorption/isothermal titration calorimetry (ITC) study that allowed highlighting the competitive adsorption mechanisms of Cd(ii), Cu(ii) and Pb(ii) on bioinspired mesoporous silica.</jats:p

Extraction and complexation of lanthanide ions by dihomooxacalix[4]arene and calix[4]arene tetraketone derivatives: An experimental and molecular dynamics investigation

International audienceLanthanide cation binding by tetraketone derivatives of p-tert-butyldihomooxacalix[4]arene (methyl 1a, tert-butyl 1b, adamantyl 1c and phenyl 1d) and of p-tert-butylcalix[4]arene (methyl 2a, adamantyl 2c and phenyl 2d), in the cone conformation, was investigated. These properties were assessed by extraction experiments of the metal picrates from water to dichloromethane and by stability constant measurements in acetonitrile by UV-vis absorption spectrophotometry. Proton NMR titrations with La3+, Eu3+ and Yb3+ cations were also performed to obtain information on the binding sites. Molecular dynamics (MD) simulations and potential of mean force (PMF) free energy calculations were carried out for ligands 1d and 2d in pure solvents and at a CH2Cl2/water interface to add further information on the complexation and extraction processes. Comparison between dihomooxacalix[4]arene and calix[4]arene ketone derivatives showed that the former are better extractants, displaying the highest percentages of extraction for Gd3+ and Yb3+ cations. Concerning complexation, all ligands studied presented high affinities for the lanthanide ions. Ligands 1b and 1d showed preference for the light La3+, while 2d displayed the strongest affinity for the heavy and smaller Yb3+. These results were also corroborated by MD simulations, which revealed specificities of ligands 1d and 2d in the binding of lanthanide cations

Naphthyl- <i>vs</i>. anthrylpyridine-2,6-dicarboxamides in cation binding studies. Synthesis and spectroscopic properties

<p>Pyridine-2,6-carboxamides bearing α- or β-naphthyl- and α- or β-anthryl residues were prepared using simple method from pyridine-2,6-carboxylic acid dichloride and the respective aromatic amines. For the obtained receptors, selective binding of lead(II) and copper(II) was found. Ion–receptor interactions were studied using UV–vis spectroscopy, spectrofluorimetry, ¹H NMR and FTIR spectroscopy. The reversible lead(II) and copper(II) binding was discussed in regard of type of aromatic residue and amide bond localisation in aromatic ring, and binding model was proposed.</p

CCDC 869234: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures