Functional modeling of the MnCAT active site with a dimanganese(III) complex of an unsymmetrical polydentate N 3 O 3 ligand

A new diMn III complex, [Mn 2 L(OAc) 2 (H 2 O)](BPh 4 )·3H 2 O (1), obtained with the unsymmetrical N 3 O 3 -ligand H 3 L = 1-[N-(2-pyridylmethyl),N-(2-hydroxybenzyl)amino]-3-[N′-(2-hydroxybenzyl),N′-(benzyl)amino]propan-2-ol, has been prepared and characterized. The unsymmetrical hexadentate ligand L 3− leads to coordination dissymmetry (dissimilar donor atoms) around each Mn ion (N 2 O 4 and NO 4 (solvent), respectively) leaving one labile site on one of the two Mn ions that facilitates interaction of the metal center with H 2 O 2 , as in Mn catalase. 1 is able to catalyze H 2 O 2 disproportionation in acetonitrile, with second-order rate constant k cat = 23.9(2) M −1 s −1 . The accessibility of the Mn II 2 state and the closeness of the two one-electron reduction processes suggest 1 employs Mn III 2 /Mn II 2 oxidation states for catalysis.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: Anxolabehere Mallart, Elodie. Université Paris Diderot - Paris 7; FranciaFil: Sabater, Laurent. Universite de Toulouse; FranciaFil: Hureau, Christelle. Universite de Toulouse; FranciaFil: Signorella, Sandra Rosanna. 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

Chemical design and synthesis of unsymmetrical diamino proligands employing a flexible route

Three new unsymmetrical diamino proligands with a central alcohol group and four different pendant arms were obtained, employing a five step synthesis. The synthesis of these compounds involves inexpensive and commercially available reagents. The versatility of the synthetic route allows accessing to compartmental diamines with two chemically different adjacent coordination chambers.Fil: Signorella, Sandra Rosanna. 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: 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; Argentin

Rationally designed mimics of antioxidant manganoenzymes: Role of structural features in the quest for catalysts with catalase and superoxide dismutase activity

Manganese catalases (MnCAT) and superoxide dismutases (MnSOD) deplete hydrogen peroxide and superoxide in cells through a ping-pong mechanism involving cyclic oxidation and reduction of the metal cofactor. In a variety of pathological situations, the generation of reactive oxygen species overwhelms the capacity of endogenous scavengers and tissues become vulnerable to damage. Due to the limited success of the use of exogenous SOD and CAT as therapeutic agents to reduce oxidative stress damage, investigations have been directed to the design of low molecular-weight antioxidant catalysts (SOD- or CAT-mimics). To disproportionate superoxide and hydrogen peroxide efficiently, the reduction potential of MnSOD and MnCAT is fine-tuned to values much lower than that of the Mn3+(aq)/Mn2+(aq) couple. In the artificial catalysts, the number and type of ligands, the local charge, the geometry around the metal, are among the factors that introduce a way of tuning the redox potential of Mn to face redox reactions. However structural and electronic factors affecting SOD activity do not parallel those controlling CAT activity. This review focus on synthetic mononuclear Mn complexes with SOD and/or CAT activity, stressing the role of ligand donor sites, endogenous acid/base groups, metal environment and second-sphere effects in the catalytic activity.Fil: Signorella, Sandra Rosanna. 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: Palopoli, Claudia Marcela. 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: 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; Argentin

A New Mononuclear Manganese(III) Complex of an Unsymmetrical Hexadentate N3O3 Ligand Exhibiting Superoxide Dismutase and Catalase-like Activity: Synthesis, Characterization, Properties and Kinetics Studies

A mononuclear MnIII complex MnL·4H2O (H3L = 1-[N-(2-pyridylmethyl),N-(2-hydroxybenzyl)amino]-3-[N′-(2-hydroxybenzyl),N′-(4- methylbenzyl)amino]propan-2-ol) has been prepared and characterized. This complex catalyzes the dismutation of superoxide efficiently, with catalytic rate constant kcat=1.7 × 106M−1 s−1 and IC50 1.26 μM, obtained through the nitro blue tetrazoliumphotoreduction inhibition superoxide dismutase assay, in aqueous solution of pH 7.8. MnL is also able to disproportionate more than 300 equivalents of H2O2 in CH3CN, with initial rate of H2O2 decomposition given by ri=kcat [MnL]2 [H2O2]and kcat = 1.32 (2) mM−2 min−1. The accessibility of the MnIV state (Ep = 0.53 V vs. saturated calomel electrode), suggests MnL employs a high-valent catalytic cycle to decompose O2?− and H2O2.Fil: Ledesma, Gabriela Nanci. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Eury, Hélène. Centre National de la Recherche Scientifique. Laboratoire de Chimie de Coordination; FranciaFil: Anxolabéhère Mallart, Elodie. Universite de Toulose - Le Mirail; FranciaFil: Hureau, Christelle. Laboratoire de Chimie de Coordination; FranciaFil: Signorella, Sandra Rosanna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentin

Convergent First Total Synthesis of Melovinone: A Densely Substituted 3-Methoxy-4-quinolone Isolated from Melochia tomentosa L

The first total synthesis of melovinone, a nonrutaceous 3-methoxy-4-quinolone alkaloid isolated from Melochia tomentosa L., is reported. The target was acquired in a convergent fashion through the Suzuki?Miyaura cross-coupling reaction between an ortho-nitrobenzoic acid acetonyl ester derivative prepared from vanillin and potassium 5-phenyl-1-pentyltrifluoroborate, obtained from β-phenethyl bromide. The coupling was followed by a chemoselective reduction of the nitro group and a microwave-assisted and AcOH-promoted cyclization with rearrangement of the resulting acetonyl anthranilate. This afforded a pseudane intermediate, which was selectively methylated on the 3-OH. The synthetic pathway enabled to reach the objective in 11 steps and 18% overall yield. The 1H NMR spectra of the synthetic and natural product were in full agreement.Fil: Arroyo Aguilar, Abel Alfredo. 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: 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: Tirloni, Bárbara. Universidade Federal de Santa Maria; BrasilFil: Kaufman, Teodoro Saul. 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: Larghi, Enrique Leandro. 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

2,2,2-trifluoroethanol-promoted access to symmetrically 3,3-disubstituted quinoline-2,4-diones

The unprecedented use of 2,2,2-trifluoroethanol as reaction solvent provided a facile and convenient access to symmetrically 3,3-disubstitued quinoline-2,4-diones in moderate to excellent yields and high regioselectivity, by reaction of 4-hydroxy-2-quinolones with electrophiles like methyl iodide, as well as benzyl and allyl bromides in the presence of K2CO3. Silver (I) oxide is required to increase the yield of the methylations.Fil: Selvero, Marcel Manke. Universidade Federal de Santa Maria; BrasilFil: 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: Abram, Ulrich. Freie Universität Berlin; AlemaniaFil: Schulz Lang, Ernesto. Universidade Federal de Santa Maria; BrasilFil: Morel, Ademir Farias. Universidade Federal de Santa Maria; BrasilFil: Larghi, Enrique Leandro. 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

Alternative ground states enable pathway switching in biological electron transfer

Electron transfer is the simplest chemical reaction and constitutes the basis of a large variety of biological processes, such as photosynthesis and cellular respiration. Nature has evolved specific proteins and cofactors for these functions. The mechanisms optimizing biological electron transfer have been matter of intense debate, such as the role of the protein milieu between donor and acceptor sites. Here we propose a mechanism regulating long-range electron transfer in proteins. Specifically, we report a spectroscopic, electrochemical, and theoretical study on WT and single-mutant CuA redox centers from Thermus thermophilus, which shows that thermal fluctuations may populate two alternative ground-state electronic wave functions optimized for electron entry and exit, respectively, through two different and nearly perpendicular pathways. These findings suggest a unique role for alternative or "invisible" electronic ground states in directional electron transfer. Moreover, it is shown that this energy gap and, therefore, the equilibrium between ground states can be fine-tuned by minor perturbations, suggesting alternative ways through which protein-protein interactions and membrane potential may optimize and regulate electron-proton energy transduction.Fil: Abriata, Luciano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: 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: Blackburn, Ninian J.. Oregon Health and Sciences University; Estados UnidosFil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Murgida, Daniel Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentin

Synthesis, structure and SOD activity of Mn complexes with symmetric Schiff base ligands derived from pyridoxal

This study describes the synthesis, crystal structure and antioxidant activity of manganese(III) complexes with Schiff-base ligands obtained from condensation of pyridoxal with alkyl diamines: [Mn(pyr2en) (H2O)2]Cl 4H2O, [Mn(pyr2en)(H2O)(CH3OH)]Cl, [Mn(pyr2pn)(H2O)2]ClO4 and [Mn2(pyr2bn)3] 4H2O, where H2pyr2en = 1,2-bis(pyridoxylidenamino)ethane, H2pyr2pn = 1,3-bis(pyridoxylidenamino)propane and H2pyr2bn = 1,4-bis(pyridoxylidenamino)butane. The four complexes catalyze the dismutation of superoxide efficiently with IC50 values in the range of 1.22?2.15 lM, evaluated through the nitro blue tetrazolium photoreduction inhibition superoxide dismutase assay, in aqueous solution of pH 7.8. The length of the alkyl spacer in the diamine fragment plays a key role in the antioxidant activity of these complexes, with [Mn(pyr2pn)(H2O)2]ClO4 showing the lowest IC50 value.Fil: Signorella, Sandra Rosanna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Daier, Veronica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Ledesma, Gabriela Nanci. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Palopoli, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Back, Davi Fernando. Universidade Federal de Santa Maria. Departamento de Química. Laboratório de Materiais Inorgânicos; BrasilFil: Lang, Ernesto S.. Universidade Federal de Santa Maria. Departamento de Química. Laboratório de Materiais Inorgânicos; BrasilFil: Rossini Kopp, Cristiéli. Universidade Federal de Santa Maria. Departamento de Química. Laboratório de Materiais Inorgânicos; BrasilFil: Ebani, Patrícia. Universidade Federal de Santa Maria. Departamento de Química. Laboratório de Materiais Inorgânicos; BrasilFil: Brum Pereira, Mateus. Universidade Federal de Santa Maria. Departamento de Química. Laboratório de Materiais Inorgânicos; BrasilFil: Giacomelli, Cristiano. Universidade Federal de Santa Maria. Departamento de Química. Laboratório de Polímeros e Colóides; BrasilFil: Piquini, Paulo Cesar. Universidade Federal de Santa Maria. Departamento de Física; Brasi