Neuroprotective effects of fluorophore-labelled manganese complexes: Determination of ROS production, mitochondrial membrane potential and confocal fluorescence microscopy studies in neuroblastoma cells

In this work, four manganese(II) complexes derived from the ligands H2L1-H2L4, that incorporate dansyl or tosyl fluorescent dyes, have been investigated in term of their antioxidant properties. Two of the manganese(II) complexes have been newly prepared using the asymmetric half-salen ligand H2L2 and the thiosemicarbazone ligand H2L3. The four organic strands and the manganese complexes have been characterized by different analytical and spectroscopic techniques. The study of the antioxidant behaviour of these two new complexes and other two fluorophore-labelled analogues was tested in SH-SY5Y neuroblastoma cells. These four model complexes 1–4 were found to protect cells from oxidative damage in this human neuronal model, by reducing the release of reactive oxygen species. Complexes 1–4 significantly improved cell survival, with levels between 79.1 ±0.8% and 130.9 ±4.1%. Moreover, complexes 3 and 4 were able to restore the mitochondrial membrane potential at 1 μM, with 4 reaching levels higher than 85%, similar to the percentages obtained by the positive control agent cyclosporin A. The incorporation of the fluorescent label in the complexes allowed the study of their ability to enter the human neuroblastoma cells by confocal microscopy.The research leading to these results has received funding from the following FEDER cofunded-grants. From Consellería de Cultura, Educaci´ on e Ordenaci´ on Universitaria, Xunta de Galicia, 2017 GRC GI-1682 (ED431C 2017/01), 2018 GRC GI-1584 (ED431C 2018/13), MetalBIO Network (ED431D 2017/01). From CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad IISCIII/PI19/001248. From Ministerio de Ciencia, Innovaci´ on y Universidades, MULTIMETDRUGS (RED2018-102471-T). From European Union, Interreg AlertoxNet EAPA-317-2016, Interreg Agritox EAPA- 998-2018, and H2020 778069-EMERTOX.S

Electrochemical Conversion of the Lignin Model Veratryl Alcohol to Veratryl Aldehyde Using Manganese(III)-Schiff Base Homogeneous Catalysts

Lignin and other colored structures need to be bleached after the Kraft process in the pulp industry. Development of environmentally-safe bleaching catalysts or electrocatalysts constitutes an attractive strategy for selective removal of lignin. Seven manganese(III)-complexes with Schiff base ligands 1–7 were synthetized and characterized by different analytical and spectroscopic techniques. The tetragonally elongated octahedral geometry for the manganese coordination sphere and the global µ-aquo dimeric structure were revealed by X-ray diffraction (XRD) studies for 1, Mn2L12(H2O)2(N(CN)2)2 (N(CN)2 = dicyanamide). Complexes 1–4 behave as more efficient peroxidase mimics as compared to 5–7. Electrochemical oxidation of the lignin model veratrylalcohol (VA) to veratrylaldehyde (VAH) is efficiently catalyzed by a type of dimanganese(III) complexes in a chlorine-free medium. The electrocatalytic reaction proceeds through the oxidation of chloride into hypochlorite at alkaline pH along with the formation of hydrogen from water as a subproductThis research was funded by Xunta de Galicia (GRC GI-1584-ED431C2018/13 Suprabioin Research Group, and MetalBIO Network ED431D 2017/01)S

Neuroprotective effects of fluorophore-labelled manganese complexes: determination of ROS production, mitochondrial membrane potential and confocal fluorescence microscopy studies in neuroblastoma cells

In this work, four manganese(II) complexes derived from the ligands H2L1-H2L4, that incorporate dansyl or tosyl fluorescent dyes, have been investigated in term of their antioxidant properties. Two of the manganese(II) complexes have been newly prepared using the asymmetric half-salen ligand H2L2 and the thiosemicarbazone ligand H2L3. The four organic strands and the manganese complexes have been characterized by different analytical and spectroscopic techniques. The study of the antioxidant behaviour of these two new complexes and other two fluorophore-labelled analogues was tested in SH-SY5Y neuroblastoma cells. These four model complexes 1–4 were found to protect cells from oxidative damage in this human neuronal model, by reducing the release of reactive oxygen species. Complexes 1–4 significantly improved cell survival, with levels between 79.1 ± 0.8% and 130.9 ± 4.1%. Moreover, complexes 3 and 4 were able to restore the mitochondrial membrane potential at 1 μM, with 4 reaching levels higher than 85%, similar to the percentages obtained by the positive control agent cyclosporin A. The incorporation of the fluorescent label in the complexes allowed the study of their ability to enter the human neuroblastoma cells by confocal microscopyThe research leading to these results has received funding from the following FEDER cofunded-grants. From Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, 2017 GRC GI-1682 (ED431C 2017/01), 2018 GRC GI-1584 (ED431C 2018/13), MetalBIO Network (ED431D 2017/01). From CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad IISCIII/PI19/001248. From Ministerio de Ciencia, Innovación y Universidades, MULTIMETDRUGS (RED2018-102471-T). From European Union, Interreg AlertoxNet EAPA-317-2016, Interreg Agritox EAPA-998-2018, and H2020 778069-EMERTOXS

Salen-manganese complexes for controlling ROS damage: Neuroprotective effects, antioxidant activity and kinetic studies

A new manganese(III) complex [MnL1(DCA)(H2O)](H2O), 1, has been prepared using the chelating ligand N,N’-bis(2-hydroxy-3-methoxybenzylidene)-1,2-diaminopropane (H2L1), and characterized by different analytical and spectroscopic techniques. The tetragonally elongated octahedral geometry for the manganese coordination sphere was revealed by X-ray diffraction studies for 1. The antioxidant behavior of this complex and other manganese(III)-salen type complexes was tested through SOD and catalase probes, and through the study of their neuroprotective effects in SH-SY5Y neuroblastoma cells. In this human neuronal model, these model complexes were found to improve cell survival in an oxidative stress model. During studies aimed to getting a better understanding of the kinetics of the processes involved in this antioxidant behavior, an important effect on the solvent in the kinetics of reaction of the complexes with H2O2 was revealed that suggests a change in the mechanism of reaction of the complexes. The kinetic data in methanol and buffered aqueous solutions correlate well with the results of the test of catalase activity, thus showing that the rate determining step in the catalytic cycle corresponds to the initial reaction of the complexes with H2O2

Estudio de la aplicabilidad de catalizadores biomiméticos con actividad redox en procesos químicos y farmacológicos

En la presente tesis se desarrollan nuevos modelos artificiales que puedan reproducir la actividad de enzimas con actividad redox. Los modelos biomiméticos desarrollados son metalocompuestos de manganeso y oro con diferentes ligandos entre los que se incluyen bases de Shiff, benzoimidazol y tiosemicarbazonas. Estos nuevos compuestos se pueden agrupar en dos grandes aplicaciones que son útiles para la industria química (descomposición fotolítica de la molécula de agua y degradación selectiva de la lignina) o farmacológica : actividad antioxidante (compuestos miméticos de la catalasa y la superóxido dismutasa) y antitumoral.2022-11-2

Pursuing the Elixir of Life: In Vivo Antioxidative Effects of Manganosalen Complexes

Manganosalen complexes are coordination compounds that possess a chelating salen-type ligand, a class of bis-Schiff bases obtained by condensation of salicylaldehyde and a diamine. They may act as catalytic antioxidants mimicking both the structure and the reactivity of the native antioxidant enzymes active site. Thus, manganosalen complexes have been shown to exhibit superoxide dismutase, catalase, and glutathione peroxidase activities, and they could potentially facilitate the scavenging of excess reactive oxygen species (ROS), thereby restoring the redox balance in damaged cells and organs. Initial catalytic studies compared the potency of these compounds as antioxidants in terms of rate constants of the chemical reactivity against ROS, giving catalytic values approaching and even exceeding that of the native antioxidative enzymes. Although most of these catalytic studies lack of biological relevance, subsequent in vitro studies have confirmed the efficiency of many manganosalen complexes in oxidative stress models. These synthetic catalytic scavengers, cheaper than natural antioxidants, have accordingly attracted intensive attention for the therapy of ROS-mediated injuries. The aim of this review is to focus on in vivo studies performed on manganosalen complexes and their activity on the treatment of several pathological disorders associated with oxidative damage. These disorders, ranging from the prevention of fetal malformations to the extension of lifespan, include neurodegenerative, inflammatory, and cardiovascular diseases; tissue injury; and other damages related to the liver, kidney, or lungs

Designing a Phosphino-Thiosemicarbazone Ligand Capable of Stabilizing Coinage Metal Ions

Thiosemicarbazones are interesting organic skeletons due to their great coordinative versatility and their interesting biological and pharmacological properties, as well as their structural diversity. However, the isolation of their monovalent coinage metal complexes, such as Cu(I), Ag(I) and Au(I), is a partially studied field, since co-ligands with soft donor atoms such as phosphines are required. In this context, our research group has been studying a new family of ligands capable of stabilizing coinage complexes without the need for auxiliary co-ligands. To this end, it was decided to incorporate a phosphorus atom into the structure of a thiosemicarbazone kernel. This work presents the design, synthesis and structural characterization of a new phosphino-thiosemicarbazone ligand

Methanolysis of 2-Cyanopyridine in the Coordination Sphere of Manganese(II). The Structure of Mn4L6Cl2 cluster (L = Methyl Picolinimidate)

The reaction of 2-cyanopyridine and Mn(II) in methanol solution led to the formation of a Mn4L6Cl2 cluster 1 containing O-methyl picolimidate as a ligand (L). The coordination of 2-cyanopyridine to the Mn(II) ion as a chelating bidentate ligand activated the CN triple bond which subsequently suffered a nucleophilic attack by CH3OH. Complex 1 was characterized by standard techniques including microanalysis, IR spectroscopy, ESI spectrometry, and magnetic susceptibility measurements. The crystal structure of 1 was determined by X-ray diffraction techniques, and the crystallographic studies revealed a planar-diamond array for 1 where the six monoanionic picolinimidates act as chelating ligands through the two nitrogen atoms

Oxidation Processes in a Phosphine-Thiocarbohydrazone Ligand

In this work, we isolated a pentadentate [P2N2S] phosphine-thiocarbohydrazone ligand H2L with a bulky phosphine group in both linker domains that undergoes an oxidation process in solution. This ligand was synthesized by a direct reaction between two equivalents of 2-diphe-nylphosphinebenzaldehyde and one equivalent of thiocarbohydrazide. Two types of crystals de-rived from this ligand were obtained and studied using X-ray diffraction spectroscopy. One structure corresponds to the monooxidized ligand H2L(O) while the other indicates a dioxidation of the compound, H2L(OO)