Modélisation du site actif de la superoxyde dismutase à manganèse (synthèse de ligands N-tripodaux, préparation de complexes de manganèse, caractérisations structurales et physico-chimiques)

Les superoxyde dismutases (SOD) protègent la cellule contre le superoxyde, en catalysant sa dismutation en dioxygène et peroxyde d'hydrogène. L'objectif de cette thèse consistait en la synthèse, la caractérisation et l'étude de la réactivité vis-à-vis du superoxyde de complexes de manganèse mimes de SOD. Les ligands choisis pour préparer ces complexes biomimétiques sont des ligands tripodaux à centre azoté, reproduisant le site actif des superoxyde dismutases à manganèse. Des complexes de manganèse ont été cristallisés et caractérisés par diffraction des rayons X, par spectroscopie UV-visible et RPE et par voltamétrie cyclique. Les structures obtenues sont variées et les propriétés magnétiques des complexes présentant des ponts carboxylato ont été étudiées. Dans le DMSO anhydre, les complexes [Mn(IPG)(CH3OH)]n(PF6)n et [Mn(BIG)(H20)2]2(PF6)2 réagissent avec le superoxyde en formant des dimères di-mu-oxo [MnIII(O)2MnIV]+, ce qui montre que le superoxyde se fixe au manganèse(II). Les complexes [Mn(BMPG)(H2O)]n(PF6)n et [Mn(TMIMA)2](PF6)2 réagissent avec le superoxyde sans former de dimères, probablement en raison de l'encombrement de leur sphère de coordination. La présence de molécules d'eau fixées au manganèse provoque un décalage dans la stœchiométrie des réactions observées. Les IC50 des complexes sont comprises entre 0,7 et 4,2.10^-6 mol.L^-1, prouvant que les complexes synthétisés sont de bons modèles de SOD en solution aqueuse. Une corrélation linéaire établie entre le potentiel anodique des complexes et l'activité montre que l'étape cinétiquement limitante est l'oxydation du manganèse(II). Enfin, par radiolyse pulsée, les constantes de vitesse k_cat ont été mesurées pour deux complexes et deux intermédiaires réactionnels, dont un adduit [MnII(IPG)O2] se formant à la vitesse de 4.10^8 L.mol^-1.s^-1, ont été mis en évidence lors de la réaction de [Mn(IPG)(CH3OH)]n(PF6)n avec le superoxyde. Un mécanisme catalytique détaillé a été proposé pour ce complexe.Superoxide dismutases (SOD) protect cells against superoxide as they catalyse its dismutation to oxygen and hydrogen peroxide. The purpose of this work was the synthesis of biomimetic manganese complexes, their characterization and the study of their reactivity towards superoxide. Nitrogen-centered tripodal ligands mimicking the active site of manganese SOD have been chosen. Manganese complexes have been crystallised and characterised by X-ray diffraction, electronic and EPR spectroscopy and by cyclic voltammetry. Obtained structures are various, and magnetic properties of complexes with carboxylato bridges have been studied. In anhydrous DMSO, the complexes [Mn(IPG)(CH3OH)]n(PF6)n and [Mn(BIG)(H2O)2]2(PF6)2 react with superoxide and form di-mu-oxo dimers [MnIII(O)2MnIV]+, showing that superoxide enters the coordination sphere of manganese(II). The complexes [Mn(BMPG)(H20)]n(PF6)n and [Mn(TMIMA)2](PF6)2 react with superoxide without the formation of any dimer, probably owing to the steric congestion of the metal environment. The presence of water linked to manganese induce a difference in the observed stoechiometry that have been rationalised. IC50 values range between 0.7 and 4.2.10^-6 mol.L^-1, demonstrating that synthesised complexes are good SOD mimics in aqueous solution. The linear correlation obtained between the anodic potential of complexes and their activity shows that the kinetically limiting step is the manganese(II) oxidation. Finally, by pulse radiolysis, kinetic constants k_cat for two complexes have been measured and two intermediates, one being an adduct [MnII(IPG)O2] formed with a rate of 4.10^8 L.mol^-1.s^-1, have been characterised during the reaction of [Mn(IPG)(CH3OH)]n(PF6)n with superoxide. A detailed catalytic mechanism have been proposed.TOULON-BU Centrale (830622101) / SudocORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

A Pulse Radiolysis Study of Catalytic Superoxide Radical Dismutation by a Manganese(II) Complex with an N-Tripodal Ligand

International audienceThis article presents a pulse radiolysis study of the reactivity of a SOD-mimic MnII complex [MnII(IPG)]+ 1 with superoxide. It uses an improved set-up with a circulating cell. It provides convergent pieces of evidence that 1 catalyses efficiently the dismutation of superoxide. Three sets of experiments are described: (1) Transient formation and decay of an adduct labeled MnOO6 were studied. (2) A multi-pulse experiment showed a reproducible behaviour upon successive superoxide pulses. (3) Superoxide decay was monitored at 270 nm to provide an overall kinetic constant. A mechanism is proposed. (\textcopyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005

Positive Allosteric Control of Guests Encapsulation by Metal Binding to Covalent Porphyrin Cages

The allosteric control of the receptor properties of two flexible covalent cages is reported. These receptors consist of two zinc(II) porphyrins connected by four linkers of two different sizes, each incorporating two 1,2,3‐triazolyl ligands. Silver(I) ions act as effectors, responsible for an on/off encapsulation mechanism of neutral guest molecules. Binding silver(I) ions to the triazoles opens the cages and triggers the coordination of pyrazine or the encapsulation of N,N′‐dibutyl‐1,4,5,8‐naphthalene diimide. The X‐ray structure of the silver(I)‐complexed receptor with short connectors is reported, revealing the hollow structure with a cavity well‐defined by two eclipsed porphyrins. Rather unexpectedly, the crystallographic structure of this receptor with pyrazine as a guest molecule showed that the cavity is occupied by two pyrazines, each binding to the zinc(II) porphyrin in a monotopic fashion.peerReviewe

New MnII Complexes with an N/O Coordination Sphere from Tripodal N-Centered Ligands - Characterization from Solid State to Solution and Reaction with Superoxide in Non-Aqueous and Aqueous Media

International audienceThe crystal structure of a dimeric bis(µ‐carboxylato)MnIIMnII complex (2) with a tetradentate N‐centered tripodal ligand, N,N‐bis[(1‐methylimidazol‐2‐yl)methyl]glycinate, is presented. The carboxylates are bridging monodentate. This complex shows some striking differences to the previously published parent compound 1 obtained with the closely related ligand N‐[(1‐methylimidazol‐2‐yl)methyl]‐N‐(2‐pyridylmethyl)glycinate. The carboxylato bridges in both structures are shown to be disrupted in solution. The reactivities in solution of compounds 1 and 2 toward superoxide were studied. In anhydrous DMSO solutions, a pathway involving a bis(µ‐oxo)MnIIIMnIV complex was identified. In water solutions, IC50 values were measured by the Fridovich test (1.7 ± 0.2 µM for 2 and 2.0 ± 0.2 µM for 1), which showed these complexes to be good superoxide scavengers. Association constants for the complexes were estimated by means of a method based on IC50 measurements of the complexes under several conditions (alone and in the presence of excess ligand). They were found to be consistent with literature data

Structural and Magnetic Properties of Carboxylato-Bridged Manganese(II) Complexes Involving Tetradentate Ligands:\, Discrete Complex and 1D Polymers. Dependence of J on the Nature of the Carboxylato Bridge

International audienceThe crystal structure of an inorganic linear polymer consisting of Mn(II) and an N-centered tripodal ligand N,N-bis(2-(6-methyl)pyridylmethyl)glycinate is presented (1, C16H20N3O3F6P1Mn1, a = 9.993(2) Å, b = 13.285(3) Å, c = 16.040(3) Å, orthorhombic, Pnam, Z = 4). The polymeric structure is ensured by carboxylato ligands connecting two Mn(II) in a rather rare syn-anti geometry. The magnetic properties of this infinite chain have been investigated, together with the magnetic properties of a dimeric Mn(II) compound (3) from a closely related ligand [N,N-bis[(1-methylimidazol-2-yl)-methyl)glycinate] involving an unusual bis(monatomic-carboxylato) bridge. The inorganic polymer 1 shows a pseudo-2D magnetic structure, with a major interaction pathway along the chain (J/k = -0.172 ± 0.005 K) and an interchain minor one (zJ`/k = -0.006 ± 0.004 K). These properties are reminiscent of those from a closely related previously reported inorganic Mn(II) polymer (2 obtained from manganese(II) and N,N-(2-pyridylmethyl)((1-methylimidazol-2-yl)methyl)glycinate). The dimer 3 shows a small antiferromagnetic coupling of J/k = -0.693 ± 0.016 K. To address the influence of the carboxylato bridging mode on the magnetic properties, these complexes are compared to a series of compounds involving carboxylato bridges of several geometries between Mn(II) ions. Carboxylato bridges induce usually antiferromagnetic coupling, with the magnitude of the interaction (|J|) increasing with the number of bridges. The J value is dependent on the bridging mode. The syn-syn bridge is an efficient pathway, even by comparison with the monatomic [(μ-\eta1-carboxylato)] bridge

Ouvrages de traitement par lagunage naturel. Filière classique et filières combinées. Guide d'exploitation

Ce guide, à destination des maîtres d'ouvrage et des exploitants, a pour objet de présenter de façon synthétique, les modalités d'exploitation d'une station de traitement des eaux usées par lagunage naturel. Il s'applique à la filière classique développée en France depuis les années 1970 et constituée de 2 à 3 bassins en série, ainsi qu'à ses filières dites « combinées ». Ces dernières associent, en fonction des objectifs de qualité recherchés, des lagunes naturelles avec des ouvrages de type culture fixée sur support fin (filtres plantés de roseaux, bassins d'infiltration-percolation). Dans le cas des ouvrages relevant d'une délégation de service public ou disposant d'un contrat de maintenance, il appartient au maître d'ouvrage de s'assurer du respect des règles d'exploitation mentionnées dans ce guide. Enfin, les recommandations de ce guide en matière d'hygiène et de sécurité ne se substituent pas à la réglementation en vigueur. Il ne peut, par ailleurs, se substituer à celui fourni par le constructeur de la station de traitement des eaux usées, ainsi qu'aux notices techniques remises par les divers fournisseurs, lorsque l'installation dispose d'équipements électromécaniques. Les présentes recommandations s'appliquent en climat tempéré. En zone tropicale, les contraintes d'exploitation peuvent être différentes

Series of Mn Complexes Based on N-Centered Ligands and Superoxide - Reactivity in an Anhydrous Medium and SOD-Like Activity in an Aqueous Medium Correlated to MnII/MnIII Redox Potentials

International audienceTwo crystal structures are described in this article: (a) the structure of a monomeric MnII complex with the tridentate N-centered N3 ligand tris[(1-methyl-2-imidazolyl)methyl]amine (TMIMA) ([MnII(TMIMA)2]2+); and (b) the structure of a monomeric MnIII complex with the tridentate N-centered N2O ligand 2-[(1-methyl-2-imidazolyl)methyl]aminophenolate (PI-)2 ([MnIII(PI)2]+) (5). The latter was isolated both in the MnII and in the MnIII state, although only MnIII crystals were successfully grown. They are part of a series of Mn complexes prepared as SOD mimics, namely [Mn(BMPG)(H2O)]+ (2) BMPG = N,N-bis[(6-methyl-2-pyridyl)methyl]glycinate, [Mn(IPG)(MeOH)]+ (3) IPG = N-[(1-methyl-2-imidazolyl)methyl]-N-(2-pyridylmethyl)glycinate, [Mn(BIG)(H2O)2]+ (4) BIG = N,N-bis[(1-methyl-2-imidazolyl)methyl]glycinate. The reactivity of MnII complexes 1 and 2 in an anhydrous medium is described and compared to that of complexes 3 and 4, the data for which was previously published. The cyclic voltammograms of the whole complex series were recorded in an aqueous medium (collidine buffer). Their SOD-like activities were estimated by the McCord-Fridovich test (IC50 with 22 μM cytc FeIII: 1.6 ± 0.1 μMol L-1 for 1, 1.2 ± 0.5 μmol L-1 for 2, 3.0 ± 0.2 μmol L-1 for 3, 3.7 ± 0.6 μmol L-1 for 4, 0.8 ± 0.1 μmol L-1 for 5). IC50 values were converted into the corresponding kinetic constant kMcCF values. A linear correlation between Ea and log(kMcCF) was obtained, indicating that in this series the conversion to MnIII is probably the rate-limiting step. This is of substantial importance for further Mn-SOD mimic design in this series. (\textcopyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005