Oxidative stress protection by manganese complexes of tail-tied aza-scorpiand ligands

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. A new polytopic ligand based in a poly-azamacrocyclic cyclophane (L3) is reported. Coordination of Mn2+ for this new ligand and two related polytopic receptors was studied by potentiometric and paramagnetic NMR spectroscopy. A remarkable antioxidant activity was evidenced for these systems by the McCord-Fridovich assay and in Escherichiacoli sodAsodB deficient bacterial cells. The three ligands 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. [Display omitted] •Double scorpiand polyazamacrocyclic manganese complexes that mimic Mn superoxide dismutase.•Water-soluble mono- and binuclear Mn(II) complex formation.•The compounds show antioxidant activity in bacteria.•The complexes show anti-inflammatory activity in macrophages.