The Critical Role of Ligand Flexibility on the Activity of Free and Immobilized Mn Superoxide Dismutase Mimics

In low-molecular-weight Mn superoxide dismutase (SOD) mimics, the ligand plays a key role in tuning the reactivity of the metal center with O2•−. We used three ligands differing in their donor sites, flexibility and/or charge, to compare the redox properties and SOD activity of the resulting Mn complexes: 1,3-bis[(pyridin-2-ylmethyl)(propargyl)amino]propane (pypapn), 1,3-bis(pyridin-2-ylmethyleneamino)propane (py2pn) and 1,4-bis(salicylidenamino)butane (H2salbn). These ligands afford Mn complexes that, in aqueous solution, exist as mononuclear species [Mn(II)(pypapn)(H2O)2]2+, [Mn(II)(py2pn)(H2O)2]2+ and [Mn(III)(salbn)(H2O)2]+. The relative reactivity of these compounds with O2•− at pH 7.8, [Mn(pypapn)(H2O)2]2+ > [Mn(salbn)(H2O)2]+ > [Mn(py2pn)(H2O)2]2+, is independent of the redox potential but strongly depends on the ligand flexibility which becomes a critical feature when the reaction occurs through an inner-sphere electron-transfer mechanism. Immobilization was used to isolate and protect the catalyst from dissociation or dimerization during catalysis. [Mn(pypapn)(H2O)2]2+, with the alkyne group, was covalently grafted to azide functionalized mesoporous silica through click chemistry, while [Mn(py2pn)(solv)2]2+ and [Mn(salbn)(solv)2]+ were encapsulated in SBA-15 mesoporous silica through ionic exchange. The retention or enhancement of the SOD activity and the improved stability of the covalently attached catalyst and the doubly charged complex encapsulated in the silica pores, make them suitable for use in aqueous media

Effect of Metal Environment and Immobilization on the Catalytic Activity of a Cu Superoxide Dismutase Mimic

The Cu(II)/Cu(I) conversion involves variation in the coordination number and geometry around the metal center. Therefore, the flexibility/rigidity of the ligand plays a critical role in the design of copper superoxide dismutase (SOD) mimics. A 1,3-Bis[(pyridin-2-ylmethyl)(propargyl)amino]propane (pypapn), a flexible ligand with an N4-donor set, was used to prepare [Cu(pypapn)(ClO4)2], a trans-Cu(II) complex whose structure was determined by the X-ray diffraction. In DMF or water, perchlorate anions are exchanged with solvent molecules, affording [Cu(pypan)(solv)2]2+ that catalyzes O2•− dismutation with a second-order rate constant kMcF = 1.26 × 107 M−1 s−1, at pH 7.8. This high activity results from a combination of ligand flexibility, total charge, and labile binding sites, which places [Cu(pypapn)(solv)2]2+ above other mononuclear Cu(II) complexes with more favorable redox potentials. The covalent anchoring of the alkyne group of the complex to azide functionalized mesoporous silica through “click” chemistry resulted in the retention of the SOD activity and improved stability. A dicationic Cu(II)-N4-Schiff base complex encapsulated in mesoporous silica was also tested as an SOD mimic, displaying higher activity than the free complex, although lower than [Cu(pypapn)(solv)2]2+. The robustness of covalently attached or encapsulated doubly charged Cu(II) complexes in a mesoporous matrix appears as a suitable approach for the design of copper-based hybrid catalysts for O2•− dismutation under physiological conditions

Insights into Second-Sphere effects on redox potentials, spectroscopic properties, and superoxide dismutase activity of manganese complexes with Schiff-Base Ligands

Six Mn-Schiff base complexes, [Mn(X-salpn)]0/+ (salpn = 1,3-bis(sal-ic-ylidenamino)propane, X = H [1], 5-Cl [2], 2,5-F2 [3], 3,5- Cl2 [4], 5-NO2 [5], 3,5-(NO2)2 [6]), were synthesized and characterized in solution, and second-sphere effects on their electrochemical and spectroscopic properties were analyzed. The six complexes catalyze the dismutation of superoxide with catalytic rate constants in the range 0.65 to 1.54 × 106 M−1 s −1 obtained through the nitro blue tetrazolium photoreduction inhibition superoxide dismutases assay, in aqueous medium of pH 7.8. In solution, these compounds possess two labile solvent molecules in the axial positions favoring coordination of the highly nucleophilic O2 •− to the metal center. Even complex 5, [Mn(5- (NO2)salpn) (OAc) (H2O)], with an axial acetate in the solid state, behaves as a 1:1 electrolyte in methanolic solution. Electron paramagnetic resonance and UV−vis monitoring of the reaction of [Mn(X-salpn)]0/+ with KO2 demonstrates that in diluted solutions these complexes behave as catalysts supporting several additions of excess O2 •−, but at high complex concentrations (≥0.75 mM) catalyst self-inhibition occurs by the formation of a catalytically inactive dimer. The correlation of spectroscopic, electrochemical, and kinetics data suggest that second-sphere effects control the oxidation states of Mn involved in the O2 •− dismutation cycle catalyzed by complexes 1−6 and modulate the strength of the Mn-substrate adduct for electron-transfer through an inner-sphere mechanism.Fil: Palopoli, Claudia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR -CONICET); Argentina.Fil: Ferreyra, Joaquín. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR -CONICET); Argentina.Fil: Conte-Daban, Amandine. Université de Toulouse. Laboratoire de Chimie de Coordination (LCC-CNRS); France.Fil: Foi, Ana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y ́ Naturales. Departamento de Química Inorgánica, Analítica y Química Física. Instituto de Química Física de los Materiales, Medio Ambiente y Energía (INQUIMAE -CONICET); Argentina.Fil: Doctorovich, Fabio. Universidad de Buenos Aires. Facultad de Ciencias Exactas y ́ Naturales. Departamento de Química Inorgánica, Analítica y Química Física. Instituto de Química Física de los Materiales, Medio Ambiente y Energía (INQUIMAE -CONICET); Argentina.Fil: Anxolabehére-Mallart, Elodie. Université Paris-Diderot. Laboratoire d'Electrochimie Moleculaire (LEM - CNRS); France.Fil: Hureau, Christelle. Université de Toulouse. Laboratoire de Chimie de Coordination (LCC-CNRS); France.Fil: Signorella, Sandra R. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR -CONICET); Argentina

Trinuclear Manganese Complexes of Unsymmetrical Polypodal Diamino N₃O₃ Ligands with an Unusual [Mn₃(μ-OR)₄]⁵⁺ Triangular Core: Synthesis, Characterization, and Catalase Activity

Two new tri-Mn^III complexes of general formula [Mn₃L₂(μ-OH)­(OAc)]­ClO₄ (H₃L = 1-[<i>N</i>-(2-pyridylmethyl),<i>N</i>-(2-hydroxybenzyl)­amino]-3-[<i>N</i>′-(2-hydroxybenzyl),<i>N</i>′-(4-X-benzyl)­amino]­propan-2-ol; <b>1</b>ClO₄, X = Me; <b>2</b>ClO₄, X = H) have been prepared and characterized. X-ray diffraction analysis of <b>1</b>ClO₄ reveals that the complex cation possesses a Mn₃(μ-alkoxo)₂(μ-hydroxo)­(μ-phenoxo)⁴⁺ core, with the three Mn atoms bound to two fully deprotonated N₃O₃ chelating L^3–, one exogenous acetato ligand, and one hydroxo bridge, the structure of which is retained upon dissolution in acetonitrile or methanol. The three Mn atoms occupy the vertices of a nearly isosceles triangle (Mn1···Mn3 = 3.6374(12) Å, Mn2···Mn3 3.5583(13) Å, and Mn1···Mn2 3.2400(12) Å), with one substitution-labile site on the apical Mn ion occupied by terminally bound monodentate acetate. Temperature-dependent magnetic susceptibility studies indicate the presence of predominant antiferromagnetic intramolecular interactions between Mn^III ions in <b>1</b>ClO₄. Complexes <b>1</b>ClO₄ and <b>2</b>ClO₄ decompose H₂O₂ at comparable rates upon initial binding of peroxide through acetate substitution, with retention of core structure during catalysis. Kinetic and spectroscopic studies suggest that these complexes employ the [Mn–(μ-oxo/aquo)–Mn]⁴⁺ moiety to activate peroxide, with the additional (μ-alkoxo)­(μ-phenoxo)­Mn­(μ-alkoxo) metallobridge carrying out a structural function

Trinuclear manganese complexes of unsymmetrical polypodal diamino N 3O3 ligands with an unusual [Mn3(μ-OR) 4]5+ triangular core: Synthesis, characterization, and catalase activity

Two new tri-MnIII complexes of general formula [Mn 3L2(μ-OH)(OAc)]ClO4 (H3L = 1-[N-(2-pyridylmethyl),N-(2-hydroxybenzyl)amino]-3-[N′-(2-hydroxybenzyl), N′-(4-X-benzyl)amino]propan-2-ol; 1ClO4, X = Me; 2ClO 4, X = H) have been prepared and characterized. X-ray diffraction analysis of 1ClO4 reveals that the complex cation possesses a Mn 3(μ-alkoxo)2(μ-hydroxo)(μ-phenoxo)4+ core, with the three Mn atoms bound to two fully deprotonated N 3O3 chelating L3-, one exogenous acetato ligand, and one hydroxo bridge, the structure of which is retained upon dissolution in acetonitrile or methanol. The three Mn atoms occupy the vertices of a nearly isosceles triangle (Mn1···Mn3 = 3.6374(12) Å, Mn2···Mn3 3.5583(13) Å, and Mn1···Mn2 3.2400(12) Å), with one substitution-labile site on the apical Mn ion occupied by terminally bound monodentate acetate. Temperature-dependent magnetic susceptibility studies indicate the presence of predominant antiferromagnetic intramolecular interactions between Mn III ions in 1ClO4. Complexes 1ClO4 and 2ClO4 decompose H2O2 at comparable rates upon initial binding of peroxide through acetate substitution, with retention of core structure during catalysis. Kinetic and spectroscopic studies suggest that these complexes employ the [Mn-(μ-oxo/aquo)-Mn]4+ moiety to activate peroxide, with the additional (μ-alkoxo)(μ-phenoxo)Mn(μ- alkoxo) metallobridge carrying out a structural function.Fil: Ledesma, Gabriela Nanci. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Anxolabéhère-Mallart, Elodie. Université Paris Diderot - Paris 7; FranciaFil: Rivière, Eric. Université Paris Sud; FranciaFil: Mallet-Ladeira, Sonia. Université Paul Sabatier; FranciaFil: Hureau, Christelle. Université Paul Sabatier; FranciaFil: Signorella, Sandra Rosanna. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentin