80 research outputs found
Novel 1-hydroxypyridin-2-one metal chelators prevent and res-cue ubiquitin proteasomal-related neuronal injury in an in vitro model of Parkinsonâs 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 compoundsâ 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
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Complexation of lanthanides, actinides and transition metal cations with a 6-(1,2,4-triazin-3-yl)-2,2â:6â,2ââ-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)-2,2â:6â,2ââ-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
1-Hydroxy-2(1H)-pyridinone-Based Chelators with Potential Catechol O-Methyl Transferase Inhibition and Neurorescue Dual Action against Parkinsonâs Disease
Two analogues of tolcapone where the nitrocatechol group has been replaced by a 1-hydroxy-2(1H)-pyridinone have been designed and synthesised. These compounds are expected to have a dual mode of action both beneficial against Parkinsonâs disease: they are designed to be inhibitors of catechol O-methyl transferase, which contribute to the reduction of dopamine in the brain, and to protect neurons against oxidative damage. To assess whether these compounds are worthy of biological assessment to demonstrate these effects, measurement of their pKa and stability constants for Fe(III), in silico modelling of their potential to inhibit COMT and bloodâbrain barrier scoring were performed. These results demonstrate that the compounds may indeed have the desired properties, indicating they are indeed promising candidates for further evaluation
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Highly efficient separation of actinides from lanthanides by a phenanthroline-derived bis-triazine ligand
The synthesis, lanthanide complexation, and solvent ex- traction of actinide(III) and lanthanide(III) radiotracers from nitric acid solutions by a phenanthroline-derived quadridentate bis-triazine ligand are described. The ligand separates Am(III) and Cm(III) from the lanthanides with remarkably high efficiency, high selectivity, and fast extraction kinetics compared to its 2,2'-bipyridine counterpart. Structures of the 1:2 bis-complexes of the ligand with Eu(III) and Yb(III) were elucidated by X-ray crystallography and force field calculations, respec-tively. The Eu(III) bis-complex is the first 1:2 bis-complex of a quadridentate bis-triazine ligand to be characterized by crystallography. The faster rates of extraction were verified by kinetics measurements using the rotating membrane cell technique in several diluents. The improved kinetics of metal ion extraction are related to the higher surface activity of the ligand at the phase interface. The improvement in the ligand's properties on replacing the bipyridine unit with a phenanthroline unit far exceeds what was anticipated based on ligand design alone
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Hydrophilic sulfonated bis-1,2,4-triazine ligands are highly effective reagents for separating actinides(iii) from lanthanides(iii) via selective formation of aqueous actinide complexes
We report the first examples of hydrophilic 6,6âČ-bis(1,2,4-triazin-3-yl)-2,2âČ-bipyridine (BTBP) and 2,9-bis(1,2,4-triazin-3-yl)-1,10-phenanthroline (BTPhen) ligands, and their applications as actinide(III) selective aqueous complexing agents. The combination of a hydrophobic diamide ligand in the organic phase and a hydrophilic tetrasulfonated bis-triazine ligand in the aqueous phase is able to separate Am(III) from Eu(III) by selective Am(III) complex formation across a range of nitric acid concentrations with very high selectivities, and without the use of buffers. In contrast, disulfonated bis-triazine ligands are unable to separate Am(III) from Eu(III) in this system. The greater ability of the tetrasulfonated ligands to retain Am(III) selectively in the aqueous phase than the corresponding disulfonated ligands appears to be due to the higher aqueous solubilities of the complexes of the tetrasulfonated ligands with Am(III). The selectivities for Am(III) complexation observed with hydrophilic tetrasulfonated bis-triazine ligands are in many cases far higher than those found with the polyaminocarboxylate ligands previously used as actinide-selective complexing agents, and are comparable to those found with the parent hydrophobic bis-triazine ligands. Thus we demonstrate a feasible alternative method to separate actinides from lanthanides than the widely studied approach of selective actinide extraction with hydrophobic bis-1,2,4-triazine ligands such as CyMe4-BTBP and CyMe4-BTPhen
SynthÚse et étude des propriétés complexantes de dérivés amides et hydroxamiques des calix[4]arÚnes 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 synthÚse et l étude de dérivés amides et hydroxyamides de calix[4]arÚnes 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 oxygÚne des amides tertiaires par des atomes de soufre conduit à des composés trÚs sélectifs pour Ag+ et Pb2+ par rapport aux cations des groupes I et II. Les dérivés acides hydroxamiques extraient trÚs 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 contrÎle 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 mĂąchefers dâincinĂ©ration dâordures mĂ©nagĂšresPartie 2 : Ă©tude sur le terrain (chaussĂ©es) et en laboratoires (lysimĂštres)
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 mĂąchefers sont les principaux rĂ©sidus (en poids) de lâincinĂ©ration des ordures mĂ©nagĂšres. Leur production, en France, sâĂ©lĂšve Ă 2,7 millions de tonnes par an. Compte tenu de la nĂ©cessitĂ© de maĂźtriser leur utilisation en technique routiĂšre, il est intĂ©ressant dâĂ©tudier cette valorisation en milieu rĂ©el par le suivi de chaussĂ©es expĂ©rimentales. Il sâagit cependant dâune dĂ©marche lourde et onĂ©reuse, dâoĂč la mise au point en complĂ©ment dâun outil de laboratoire (lysimĂštre) permettant de simuler diffĂ©rentes conditions de valorisation. La valorisation en conditions rĂ©elles dâun mĂąchefer a Ă©tĂ© Ă©tudiĂ©e grĂące au suivi de deux chaussĂ©es expĂ©rimentales sur une durĂ©e de 3 ans. Dâune maniĂšre gĂ©nĂ©rale, un faible apport des mĂąchefers a Ă©tĂ© mesurĂ© sur la composition des eaux de percolation. Une faible toxicitĂ© des percolats a Ă©tĂ© observĂ©e en fin de suivi. Les diffĂ©rents essais effectuĂ©s en lysimĂštres ont permis de montrer une bonne reproductibilitĂ© de la composition des percolats. La corrĂ©lation avec les chaussĂ©es nâa pas encore pu ĂȘtre clairement Ă©tablie
Valorisation de mĂąchefers dâincinĂ©ration dâordures mĂ©nagĂšresPartie 1 : caractĂ©risation des mĂąchefers
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 mĂ©nagĂšres sont incinĂ©rĂ©es produisant 2,7millions de tonnes de mĂąchefers par an. Il est possible dâutiliser ce dĂ©chet en technique routiĂšre sâil rĂ©pond Ă des critĂšres bien spĂ©cifiques (circulaire ministĂ©rielle du 9 mai 1994). Il est donc important de connaĂźtre les caractĂ©ristiques des mĂąchefers avant de rendre effective leur valorisation. Lâobjet de ce travail est dâabord de caractĂ©riser un mĂąchefer dâincinĂ©ration dâordures mĂ©nagĂšres destinĂ© Ă ĂȘtre valorisĂ©. Les caractĂ©ristiques gĂ©otechniques et la faible fraction lixiviable dĂ©terminĂ©es sur ce mĂąchefer permettent, selon la rĂ©glementation, son utilisation en technique routiĂšre. Par ailleurs, la dĂ©termination de sa composition Ă©lĂ©mentaire a montrĂ© la prĂ©sence dâĂ©lĂ©ments majeurs (Si, Ca, Al, S), mineurs (Cr, Mn, Cu, Pb, Ni, Zn) et traces (As, Cd, Hg, Se) dont les diffĂ©rentes teneurs ont Ă©tĂ© quantifiĂ©es
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