Application of metal complexes as biomimetic catalysts on glycerol oxidation

Two biomimetic complexes were evaluated as catalysts in the H2O2 mediated oxidation of glycerol, namely a peroxidase mimetic Fe(III) protoporphyrin complex (hematin) and the superoxide-dismutase mimetic complex of Mn(III) with 1,3-bis(5-sulphonatesalycilidenamino) propane (MnL−). Catalysis was targeted to glyceraldehyde since antimicrobial power was proved for it. Glyceraldehyde evolved at a higher rate than the uncatalyzed reaction only with hematin acid treated solutions and kinetics were typical of a radical mechanism. Nonetheless, glycerol conversions were low. H2O2 bleached hematin and the immobilization on a porous matrix could not prevent this. Meanwhile, the catalatic activity of hematin was high but its peroxidatic activity was inhibited at pH > 8. Thus, the coordination of hematin compound I to H2O2 over glycerol may be the preferred route with the accumulation of peroxy radicals, able to degrade the porphyrinic ring -with probable iron releasing- but also contributing to glycerol oxidation. On the other hand, a prompt decay with time of the catalatic and peroxidatic activities of MnL− was observed, which was improved by the addition of dimethylsulfoxide (DMSO), dimethylformamide (DMF) or acetone to the basic buffer system. Finally, EPR spectroscopy of MnL− supported the hypothesis of the formation of an inactive bis-oxo-bridged Mn(IV)Mn(IV) dimer upon addition of H2O2.publishedVersionFil: Parodi, Adrián Rodrigo. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada (IPQA); Argentina.Fil: Parodi, Adrián Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada (IPQA); Argentina.Fil: Merlo, Carolina. Universidad Nacional de Córdoba. Instituto Multidisciplinario de Biología Vegetal (IMBIV); Argentina.Fil: Merlo Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto Multidisciplinario de Biología Vegetal (IMBIV); Argentina.Fil: Córdoba, Agostina. Universidad Tecnológica Nacional - Facultad Regional Córdoba (U.T.N – F.R.C). Centro de Investigación y Tecnología Química “Prof. Dr. Oscar A. Orio” (CITeQ); Argentina.Fil: Córdoba, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Centro de Investigación y Tecnología Química “Prof. Dr. Oscar A. Orio” (CITeQ); Argentina.Fil: Palopoli, Claudia. Universidad Nacional de Rosario. Instituto de Química Rosario (IQUIR); Argentina.Fil: Palopoli, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Centro Científico Tecnológico (CCT Rosario). Instituto de Química Rosario (IQUIR); Argentina.Fil: Ferreyra, Joaquín. Universidad Nacional de Rosario. Instituto de Química Rosario (IQUIR); Argentina.Fil: Ferreyra, Joaquín. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Centro Científico Tecnológico (CCT Rosario). Instituto de Química Rosario (IQUIR); Argentina.Fil: Signorella, Sandra. Universidad Nacional de Rosario. Instituto de Química Rosario (IQUIR); Argentina.Fil: Signorella, Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Centro Científico Tecnológico (CCT Rosario). Instituto de Química Rosario (IQUIR); Argentina.Fil: Ferreira, María Luján. Universidad Nacional del Sur (UNS). Planta Piloto de Ingeniería Química (PLAPIQUI); Argentina.Fil: Ferreira, María Luján. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Planta Piloto de Ingeniería Química (PLAPIQUI); Argentina.Fil: Magario, Ivana. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada (IPQA); Argentina.Fil: Magario, Ivana. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada (IPQA); Argentina

Synthesis, characterization, and reactivity studies of a water-soluble bis(alkoxo)(carboxylato)- bridged diMnIII complex modeling the active site in catalase

A new diMnIII complex, Na[Mn2(5-SO3-salpentO)(μ-OAc)(μ-OMe)(H2O)]·4H2O, where 5-SO3-salpentOH = 1,5-bis(5-sulphonatosalicylidenamino)pentan-3-ol, has been prepared and characterized. ESI-mass spectrometry, paramagnetic 1H NMR, EPR and UV-visible spectroscopic studies on freshly prepared solutions of the complex in methanol and 9 : 1 methanol–water mixtures showed that the compound retains the triply bridged bis(μ-alkoxo)(μ-acetato)Mn23+ core in solution. In the 9 : 1 methanol–water mixture, slow substitution of acetate by water molecules took place, and after one month, the doubly bridged diMnIII complex, [Mn2(5-SO3-salpentO)(μ-OMe)(H2O)3]·5H2O, formed and could be characterized by X-ray diffraction analysis. In methanolic or aqueous basic media, acetate shifts from a bridging to a terminal coordination mode, affording the highly stable [Mn2(5-SO3-salpentO)(μ-OMe)(OAc)]− anion. The efficiency of the complex in disproportionating H2O2 depends on the solvent and correlates with the stability of the complex (towards metal dissociation) in each medium: basic buffer > aqueous base > water. The buffer preserves the integrity of the catalyst and the rate of O2 evolution remains essentially constant after successive additions of excess of H2O2. Turnovers as high as 3000 mol H2O2 per mol of catalyst, without significant decomposition and with an efficiency of kcat/KM = 1028 M−1 s−1, were measured for the complex in aqueous buffers of pH 11. Kinetic and spectroscopic results suggest a catalytic cycle that runs between MnIII2 and MnIV2 oxidation states, which is consistent with the low redox potential observed for the MnIII2/MnIIIMnIV couple of the catalyst in basic medium.Fil: Palopoli, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Duhayon, Carine. Universite de Toulose - Le Mirail; Francia. Laboratoire de Chimie de Coordination; FranciaFil: Tuchagues, Jean Pierre. Universite de Toulose - Le Mirail; Francia. 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

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

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

Effect of coordination dissymmetry on the catalytic activity of manganese catalase mimics

International audienceTwo mixed-valence Mn(II)Mn(III) complexes, [Mn2L1(OAc)2(H2O)]BPh4·2.5H2O and [Mn2L2(OAc)2]·4H2O, obtained with unsymmetrical N4O2-hexadentate L1(2−) (H2L1 = 2-(N,N-bis(2-(pyridylmethyl)aminomethyl)-6-(N-(2-hydroxybenzyl)benzylaminomethyl)-4-methylphenol) and N4O3-heptadentate L2(3−) (NaH2L2 = 2-(N,N-bis(2-(pyridylmethyl)aminomethyl)-6-(N′-(2-hydroxybenzyl)(carboxymethyl)aminomethyl)-4-methylphenol sodium salt) ligands, have been prepared and characterized. Both complexes share a μ-phenolate-bis(μ-acetate)Mn(II)Mn(III) core and N3O3-coordination sphere around the Mn(II) ion, but differ in the donor groups surrounding Mn(III) (NO4(solvent) and NO5). In non-protic solvents, these two complexes are able to disproportionate at least 3600 equiv. of H2O2 without significant decomposition, with first-order dependence on catalyst and saturation kinetics on [H2O2]. Spectroscopic monitoring of the reaction mixtures revealed the two complexes disproportionate H2O2 employing a different redox cycle, with retention of dinuclearity. The higher catalytic efficiency of [Mn2L2(OAc)2] was rationalized in terms of the larger labilizing effect of the heptadentate ligand that favors the acetate-shift and the replacement of the non-coordinating benzyl arm of L1 by a carboxylate arm in L2 which facilitates the formation of the catalyst-H2O2 adduct, placing [Mn2L2(OAc)2] as the most efficient among the phenolate-bridged diMn catalysts based on the kcat/KM criterion

Catalase activity of diMnIII complexes with the [Mn2(m-O2C2H3)(m-OL)(m-OX)]3+ core (L = polydentate ligand; X = CH3 or OC2H3): Structural features that control catalysis

Mn catalases catalyze disproportionation of H2O2 into H2O and O2 by using a Mn2(m-O2CR)(m-O/OH/H2O)2 structural unit that cycles between the MnII2 and MnIII2 oxidation states. Because of the fast kinetics of this enzymatic reaction each independent step of the catalytic cycle has not yet been characterized. In this context, biomimetic compounds provide a unique way for testing mechanisms in these enzymes. The fine-tuning of Mn redox states is a critical feature when using artificial compounds to model the enzymatic activity. We have evidenced some of the key structural factors that control the oxidation states of Mn during H2O2 decomposition by comparing the catalase activity of diMn complexes of 1,3-bis[(2-hydroxybenzyl)(2-pyridylmethyl)amino]propan-2-ol (hbpmpnOH) with that of diMn compounds including other dinucleating ligands. New complexes, [Mn2(hbpmpnO)(m-O2C2H3)(m-OCH3)]BPh4 and [Mn2(X-hbpmpnO)(m-O2C2H3)2]BPh4 (X = Cl, OMe), were synthesized and characterized, and their catalase-like activity was evaluated. These compounds possess a triply bridged diMnIII core, including either bis(m-alkoxo)(m-carboxylato) or (m-alkoxo)bis(m-carboxylato) bridges, with the remaining coordination sites of the two Mn’s occupied by the six donor atoms of the polydentate ligand. These complexes show catalytic activity toward disproportionation of H2O2, without a lag phase and first-order kinetic on [catalyst]. Spectroscopic monitoring of the H2O2 disproportionation reaction showed that these diMn compounds dismutate H2O2 by a mechanism involving redox cycling between Mn2II/Mn2III levels with retention of dinuclearity during catalysis. A correlation between the electronic properties of the different ring substituents, the redox potentials of the dinuclear complexes and their catalase activity was evidenced. Comparison of the structure, kinetic parameters and redox potentials of the present diMn compounds with those of other diMn complexes also including polydentate ligands with a central bridging alkoxo revealed that the oxidation states of Mn during the catalytic cycle are not critically dependent on the redox potentials of the catalyst but strongly depend on the peroxide binding mode to the metal centre(s).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: Tuchagues, Jean Pierre. Laboratoire de Chimie de Coordination, UPR CNRS 8241; FranciaFil: Moreno, Diego Martin. 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; Argentin

Synthesis, characterization and superoxide dismutase activity of a biomimetic Mn(III) complex covalently anchored to mesoporous silica

A mononuclear Mn(III) complex of a clickable ligand, [Mn(hbpapn)(H2O)2]ClO4·4.5H2O, where H2hbpapn = 1,3-bis[(2-hydroxybenzyl)(propargyl)amino]propane, has been prepared and fully characterized. The complex catalyzes the dismutation of superoxide employing a Mn(III)/Mn(IV) redox cycle, with catalytic rate constant of 3.9 × 106 M−1 s−1 determined through the nitro blue tetrazolium photoreduction inhibition assay, in aqueous medium of pH 7.8. The alkyne function of the ligand was used for the covalent attachment of the catalyst to azide modified mesoporous silicas with different texture and morphology, through click chemistry. In these materials the catalyst is essentially linked to the inner pore walls, isolated and protected from the external medium. The hybrid materials can be recycled, and retain or improve the superoxide dismutase activity of the free catalyst with the pore size of the solid matrix playing a role on the activity of the catalyst.Fil: Richezzi, Micaela. 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: Pellegri, Nora Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Física de Rosario. Universidad Nacional de Rosario. Instituto de Física de Rosario; ArgentinaFil: 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

FEDRO: a software tool for the automatic discovery of candidate ORFs in plants with c →u RNA editing

Abstract Background RNA editing is an important mechanism for gene expression in plants organelles. It alters the direct transfer of genetic information from DNA to proteins, due to the introduction of differences between RNAs and the corresponding coding DNA sequences. Software tools successful for the search of genes in other organisms not always are able to correctly perform this task in plants organellar genomes. Moreover, the available software tools predicting RNA editing events utilise algorithms that do not account for events which may generate a novel start codon. Results We present Fedro, a Java software tool implementing a novel strategy to generate candidate Open Reading Frames (ORFs) resulting from Cytidine to Uridine (c→u) editing substitutions which occur in the mitochondrial genome (mtDNA) of a given input plant. The goal is to predict putative proteins of plants mitochondria that have not been yet annotated. In order to validate the generated ORFs, a screening is performed by checking for sequence similarity or presence in active transcripts of the same or similar organisms. We illustrate the functionalities of our framework on a model organism. Conclusions The proposed tool may be used also on other organisms and genomes. Fedro is publicly available at http://math.unipa.it/rombo/FEDRO

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