title: Oxidative stress protection by manganese complexes of tail-tied aza-scorpiand ligands.
abstract: The Mn2+coordination chemistry of double scorpiand ligands in which two polyazacyclophane macrocycles have been connected by pyridine, phenanthroline and bipyridine spacers has been studied by potentiometry, paramagnetic NMR and electrochemistry. All ligands show high stability with Mn2+and the complexes were formed in a wide pH range. DFT calculations support the structures and coordination geometries derived from the study. A remarkable antioxidant activity was evidenced for these systems by the McCord-Fridovich assay and in Escherichiacoli sodAsodB deficient bacterial cells. The three systems were tested as anti-inflammatory drugs in human macrophages measuring the accumulation of cytokines upon lipopolysaccharide (LPS) pro-inflammatory effect. All complexes showed anti-inflammatory effect, being [Mn2L1]4+the most efficient one.
authors.affiliation: Instituto de Ciencia Molecular, Universidad de Valencia, C/Catedrático José Beltrán 2, 46980 Paterna, Valencia, Spain; Department of Chemistry, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Jorge
authors.initials: J
authors.lastname: González-García
authors.affiliation: Instituto de Ciencia Molecular, Universidad de Valencia, C/Catedrático José Beltrán 2, 46980 Paterna, Valencia, Spain.
authors.forename: Àlvar
authors.initials: À
authors.lastname: Martínez-Camarena
authors.affiliation: Instituto de Ciencia Molecular, Universidad de Valencia, C/Catedrático José Beltrán 2, 46980 Paterna, Valencia, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Verdejo
authors.affiliation: Instituto de Ciencia Molecular, Universidad de Valencia, C/Catedrático José Beltrán 2, 46980 Paterna, Valencia, Spain.
authors.forename: M Paz
authors.initials: MP
authors.lastname: Clares
authors.affiliation: Instituto de Ciencia Molecular, Universidad de Valencia, C/Catedrático José Beltrán 2, 46980 Paterna, Valencia, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Soriano
authors.affiliation: Instituto de Ciencia Molecular, Universidad de Valencia, C/Catedrático José Beltrán 2, 46980 Paterna, Valencia, Spain. Electronic address: enrique.garcia-es@uv.es.
authors.forename: Enrique
authors.initials: E
authors.lastname: García-España
authors.affiliation: Departamento de Química Inorgánica, Facultad de Química, Universidad de Valencia, C/Dr. Moliner 50, 46100 Burjassot, Valencia, Spain. Electronic address: hermas.jimenez@uv.es.
authors.forename: Hermás R
authors.initials: HR
authors.lastname: Jiménez
authors.affiliation: Departamento de Química Analítica, Facultad de Química, Universidad de Valencia, C/Dr. Moliner 50, 46100 Burjassot, Valencia, Spain. Electronic address: antonio.domenech@uv.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Doménech-Carbó
authors.affiliation: Departamento de Química Física, Facultad de Química, Universidad de Valencia, C/Dr. Moliner 50, 46100 Burjassot, Valencia, Spain. Electronic address: roberto.tejero@uv.es.
authors.forename: Roberto
authors.initials: R
authors.lastname: Tejero
authors.affiliation: Unitat de Recerca, Hospital Joan XXIII, Institut d'Investigació Sanitaria Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Calvo
authors.affiliation: Unitat de Recerca, Hospital Joan XXIII, Institut d'Investigació Sanitaria Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Briansó-Llort
authors.affiliation: Unitat de Recerca, Hospital Joan XXIII, Institut d'Investigació Sanitaria Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Serena
authors.affiliation: Unitat de Recerca, Hospital Joan XXIII, Institut d'Investigació Sanitaria Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Trefler
authors.affiliation: Unitat de Recerca, Hospital Joan XXIII, Institut d'Investigació Sanitaria Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain. Electronic address: agarciae.hj23.ics@gencat.cat.
authors.forename: Antonio
authors.initials: A
authors.lastname: Garcia-España
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008345:Manganese / Q000737:chemistry / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001426:Bacterial Proteins; D056831:Coordination Complexes; D008345:Manganese; C095500:SodA protein, Bacteria; C087504:SodB protein, Bacteria; D013482:Superoxide Dismutase
keywords: Anti-inflammatory activity; Antioxidant activity; Bacteria; Double polyazamacrocyclic scorpiands; Mn(2+) complexes