Pabellon, Argentina
Pabellon, Argentina

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Alvarez-Paggi D.,Analitica y Quimica Fisica | Alvarez-Paggi D.,CONICET | Castro M.A.,Analitica y Quimica Fisica | Castro M.A.,CONICET | And 5 more authors.
Journal of the American Chemical Society | Year: 2013

We have employed a combination of protein film voltammetry, time-resolved vibrational spectroelectrochemistry and molecular dynamics simulations to evaluate the electron-transfer reorganization free energy (λ) of cytochrome c (Cyt) in electrostatic complexes that mimic some basic features of protein-protein and protein-lipid interactions. The results reveal the existence of two native-like conformations of Cyt that present significantly different λ values. Conversion from the high to the low λ forms is triggered by electrostatic interactions, and involves the rupture of a weak H-bond between first-(M80) and second-sphere (Y67) ligands of the heme iron, as a distinctive feature of the conformational switch. The two flexible Ω loops operate as transducers of the electrostatic signal. This fine-tuning effect is abolished in the Y67F Cyt mutant, which presents a λ value similar to the WT protein in electrostatic complexes. We propose that interactions of Cyt with the natural redox partner proteins activate a similar mechanism to minimize the reorganization energy of interprotein electron transfer. © 2013 American Chemical Society.

Kuzmanich G.,University of California at Los Angeles | Simoncelli S.,Analitica y Quimica Fisica | Gard M.N.,University of California at Los Angeles | Spanig F.,The Interdisciplinary Center | And 3 more authors.
Journal of the American Chemical Society | Year: 2011

We report an efficient triplet state self-quenching mechanism in crystals of eight benzophenones, which included the parent structure (1), six 4,4′-disubstituted compounds with NH 2 (2), NMe 2 (3), OH (4), OMe (5), COOH (6), and COOMe (7), and benzophenone-3,3′,4, 4′-tetracarboxylic dianhydride (8). Self-quenching effects were determined by measuring their triplet-triplet lifetimes and spectra using femtosecond and nanosecond transient absorption measurements with nanocrystalline suspensions. When possible, triplet lifetimes were confirmed by measuring the phosphorescence lifetimes and with the help of diffusion-limited quenching with iodide ions. We were surprised to discover that the triplet lifetimes of substituted benzophenones in crystals vary over 9 orders of magnitude from ca. 62 ps to 1 ms. In contrast to nanocrystalline suspensions, the lifetimes in solution only vary over 3 orders of magnitude (1-1000 μs). Analysis of the rate constants of quenching show that the more electron-rich benzophenones are the most efficiently deactivated such that there is an excellent correlation, ρ = -2.85, between the triplet quenching rate constants and the Hammet θ + values for the 4,4′ substituents. Several crystal structures indicate the existence of near-neighbor arrangements that deviate from the proposed ideal for "n-type" quenching, suggesting that charge transfer quenching is mediated by a relatively loose arrangement. © 2011 American Chemical Society.

Perec M.,Analitica y Quimica Fisica | Baggio R.,Comision Nacional de la Energia Atomica
Acta Crystallographica Section E: Structure Reports Online | Year: 2010

The title centrosymmetric bimetallic complex, [Cu2(C 2H3O2)4(C6H 6N2O)4], is composed of two copper(II) cations, four acetate anions and four isonicotinamide (INA) ligands. The asymmetric unit contains one copper cation to which two acetate units bind asymmetrically; one of the Cu - O distances is rather long [2.740 (2) Å], almost at the limit of coordination. These Cu - O bonds define an equatorial plane to which the Cu - N bonds to the INA ligands are almost perpendicular, the Cu - N vectors subtending angles of 2.4 (1) and 2.3 (1)° to the normal to the plane. The metal coordination geometry can be described as a slightly distorted trigonal bipyramid if the extremely weak Cu - O bond is disregarded, or as a highly distorted square bipyramid if it is not. The double acetate bridge between the copper ions is not coplanar with the CuO4 equatorial planes, the dihedral angle between the (O - C - O)2 and O - Cu - O groups being 34.3 (1)°, resulting in a sofa-like conformation for the 8-member bridging loop. In the crystal, N - H⋯O hydrogen bonds occur, some of which generate a head-to tail-linkage between INA units, giving raise to chains along [101]; the remaining ones make inter-chain contacts, defining a three-dimensional network. There are in addition a number of C - H⋯O bonds involving aromatic H atoms. Probably due to steric hindrance, the aromatic rings are not involved in significant π⋯π inter-actions.

Rodriguez-Granillo A.,Rice University | Crespo A.,Rice University | Crespo A.,Merck And Co. | Estrin D.A.,Analitica y Quimica Fisica | And 2 more authors.
Journal of Physical Chemistry B | Year: 2010

The molecular details of how copper (Cu) is transferred from the human Cu chaperone Atox1 to metalbinding domains (MBDs) of P1B-type ATPases are still unclear. Here, we use a computational approach, employing quantum mechanics/molecular mechanics (QM/MM) methods, to shed light on the reaction mechanism [probable intermediates, Cu(I) coordination geometries, activation barriers, and energetics] of Cu(I) transfer from Atox1 to the fourth MBD of Wilson disease protein (WD4). Both Atox1 and WD4 have solvent-exposed metal-binding motifs with two Cys residues that coordinate Cu(I). After assessing the existence of all possible 2-, 3- and 4-coordinate Cu-intermediate species, one dominant reaction path emerged. First, without activation barrier, WD4's Cys1 binds Cu(I) in Atox1 to form a 3-coordinated intermediate. Next, with an activation barrier of about 9.5 kcal/mol, a second 3-coordinated intermediate forms that involves both of the Cys residues in WD4 and Cys1 of Atox1. This species can then form the product by decoordination of Atox1's Cys1 (barrier of about 8 kcal/mol). Overall, the Cu-transfer reaction from Atox1 to WD4 appears to be kinetically accessible but less energetically favorable (△E = 7.7 kcal/mol). Our results provide unique insights into the molecular mechanism of protein-mediated Cu(I) transfer in the secretory pathway and are in agreement with existing experimental data. © 2010 American Chemical Society.

De La Llave E.,Analitica y Quimica Fisica | Molinero V.,University of Utah | Scherlis D.A.,Analitica y Quimica Fisica
Journal of Physical Chemistry C | Year: 2012

The liquid-vapor transition in cylindrical pores is studied as a function of pore size and hydrophilicity through molecular dynamics simulations with the mW coarse-grained model of water. We identify two distinct filling mechanisms, depending on whether the water-pore interaction is smaller or larger than the water-water interaction. In the former case (that we term hydrophobic pore), the formation of the condensed phase proceeds gradually with filling, through the nucleation of a water cluster which grows toward the center of the cavity. In hydrophilic pores, instead, the condensed phase develops in conditions of supersaturation, which in principle become more extreme with increasing pore radius and surface affinity. For highly hydrophilic interfaces (those with adsorption energy for water above 10 kcal/mol), the equilibrium and dynamical properties of water in confinement turn out to be practically independent of water affinity. © 2011 American Chemical Society.

Capdevila D.A.,Analitica y Quimica Fisica | Marmisolle W.A.,Analitica y Quimica Fisica | Tomasina F.,University of the Republic of Uruguay | Demicheli V.,University of the Republic of Uruguay | And 3 more authors.
Chemical Science | Year: 2015

Cytochrome c (Cyt-c) has been previously shown to participate in cardiolipin (CL) oxidation and, therefore, in mitochondrial membrane permeabilization during the early events of apoptosis. The gain in this function has been ascribed to specific CL/Cyt-c interactions. Here we report that the cationic protein Cyt-c is also able to interact electrostatically with the main lipid components of the mitochondrial membranes, the zwitterionic lipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE), through the mediation of phosphate anions that bind specifically to amino groups in the surfaces of protein and model membranes. In these complexes, Cyt-c reacts efficiently with H2O2 at submillimolar levels, which oxidizes the sulfur atom of the axial ligand Met80. The modified protein is stable and presents significantly enhanced peroxidatic activity. Based on these results, we postulate that the rise of H2O2 concentrations to the submillimolar levels registered during initiation of the apoptotic program may represent one signaling event that triggers the gain in peroxidatic function of the Cyt-c molecules bound to the abundant PE and PC membrane components. As the activated protein is a chemically stable species, it can potentially bind and oxidize important targets, such as CL. This journal is © The Royal Society of Chemistry.

Zeida A.,Analitica y Quimica Fisica | Reyes A.M.,University of the Republic of Uruguay | Lebrero M.C.G.,University of Buenos Aires | Radi R.,University of the Republic of Uruguay | And 2 more authors.
Chemical Communications | Year: 2014

Peroxiredoxins (Prxs) catalyze the reduction of peroxides, a process of key relevance in a variety of cellular processes. The first step in the catalytic cycle of all Prxs is the oxidation of a cysteine residue to sulfenic acid, which occurs 103-107 times faster than in free cysteine. We present an experimental kinetics and hybrid QM/MM investigation to explore the reaction of Prxs with H2O2 using alkyl hydroperoxide reductase E from Mycobacterium tuberculosis as a Prx model. We report for the first time the thermodynamic activation parameters of H2O2 reduction using Prx, which show that protein significantly lowers the activation enthalpy, with an unfavourable entropic effect, compared to the uncatalyzed reaction. The QM/MM simulations show that the remarkable catalytic effects responsible for the fast H2O2 reduction in Prxs are mainly due to an active-site arrangement, which establishes a complex hydrogen bond network activating both reactive species. This journal is © the Partner Organisations 2014.

De Candia A.G.,Analitica y Quimica Fisica | Marcolongo J.P.,Analitica y Quimica Fisica | Etchenique R.,Analitica y Quimica Fisica | Slep L.D.,Analitica y Quimica Fisica
Inorganic Chemistry | Year: 2010

trans-[(NC)Ru(py) 4(μ-CN)Ru(py) 4(NO)] 3+ (py = pyridine) is a stable species in aqueous solution. It displays an intense absorption in the visible region of the spectrum (λ max = 518 nm; ε max = 6100 M -1 cm -1), which turns this compound into a promising agent for the photodelivery of NO. The quantum yield for the photodelivery process resulting from irradiation with 455 nm visible light was found experimentally to be (0.06 ± 0.01)×10 -3 mol einstein -1, almost 3 orders of magnitude smaller than that in the closely related cis-[RuL(NH 3) 4(μ-pz) Ru(bpy) 2(NO)] 5+ species (L = NH 3 or pyridine, pz = pyrazine, bpy = 2,2′-bipyridine; φ NO = 0.02-0.04 mol einstein -1 depending on L) and also much smaller than the one in the mononuclear compound trans-[ClRu(py) 4(NO)] 2+ (φ NO = (1.63 ± 0.04)×10 -3 mol einstein -1). DFT computations provide an electronic structure picture of the photoactive excited states that helps to understand this apparently abnormal behavior. © 2010 American Chemical Society.

Suarez S.A.,Analitica y Quimica Fisica | Fonticelli M.H.,National University of La Plata | Rubert A.A.,National University of La Plata | De La Llave E.,Analitica y Quimica Fisica | And 4 more authors.
Inorganic Chemistry | Year: 2010

Nitroxyl (HNO) is a small short-lived molecule for which it has been suggested that it could be produced, under certain cofactors conditions, by nitric oxide (NO) synthases. Biologically relevant targets of HNO are heme proteins, thiols, molecular oxygen, NO, and HNO itself. Given the overlap of the targets and reactivity between NO and HNO, it is very difficult to discriminate their physiopathological role conclusively, and accurate discrimination between them still remains critical for interpretation of the ongoing research in this field. The high reactivity and stability of cobalt(II) porphyrins toward NO and the easy and efficient way of covalently joining porphyrins to electrodes through S-Au bonds prompted us to test cobalt(II) 5,10,15,20-tetrakis[3-(p- acetylthiopropoxy)phenyl]porphyrin [Co(P)], as a possible candidate for the electrochemical discrimination of both species. For this purpose, first, we studied the reaction between NO, NO donors, and commonly used HNO donors, with Co II(P) and Co III(P). Second, we covalently attached Co II(P) to gold electrodes and characterized its redox and structural properties by electrochemical techniques as well as scanning tunneling microscopy, X-ray photoelectron spectroscopy, and solid-state density functional theory calculations. Finally, we studied electrochemically the NO and HNO donor reactions with the electrode-bound Co(P). Our results show that Co(P) is positioned over the gold surface in a lying-down configuration, and a surface effect is observed that decreases the Co III(P) (but not Co III(P)NO -) redox potential by 0.4 V. Using this information and when the potential is fixed to values that oxidize Co III(P)NO - (0.8 V vs SCE), HNO can be detected by amperometric techniques. Under these conditions, Co(P) is able to discriminate between HNO and NO donors, reacting with the former in a fast, efficient, and selective manner with concomitant formation of the Co III(P)NO - complex, while it is inert or reacts very slowly with NO donors. © 2010 American Chemical Society.

Boron I.,Analitica y Quimica Fisica | Suarez S.A.,Analitica y Quimica Fisica | Doctorovich F.,Analitica y Quimica Fisica | Marti M.A.,Analitica y Quimica Fisica | Bari S.E.,Analitica y Quimica Fisica
Journal of Inorganic Biochemistry | Year: 2011

The selectivity of MnIII/II porphyrinates toward nitroxyl or nitric oxide donors provides a convenient starting point for the development of new materials for the speciation of these nitrogen-containing redox relatives. In the present report, we describe the insertion of MnIII protoporphyrinate IX in apomyoglobin and its chemical behavior toward HNO or NO donors, either under anaerobic or aerobic conditions. For comparison and discussion, the MnIII porphyrinate, devoid of the protein matrix, was studied in parallel. The MnIII reconstituted globin successfully reacted with the nitroxyl donor trioxodinitrate, while it was unreactive toward NO or NO donors, in good agreement with previously reported data on water soluble MnIII porphyrinates. The estimated association rate constant for the reaction with the nitroxyl donor was of the same order of magnitude for the reconstituted globin and the free porphyrinate, suggesting that the protein environment is not involved in the reaction mechanism. In contrast, the reaction product exhibited enhanced stability in the presence of dioxygen only when the porphyrinate was included in the protein matrix; this feature is ascribed to the role of the distal residues on the metal centered reactivity. This behavior is required for spectroscopic detection under biologically relevant conditions. © 2011 Elsevier Inc.

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