Manganese(II) Complexes with the Non-steroidal Anti-Inflammatory Drug Tolfenamic Acid: Structure and Biological Perspectives

Manganese­(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid (Htolf) with the nitrogen-donor heterocyclic ligands 1,10-phenanthroline (phen), pyridine (py), or 2,2′-bipyridylamine (bipyam) and/or the oxygen-donor ligands H<sub>2</sub>O or <i>N</i>,<i>N</i>-dimethylformamide (DMF) have been synthesized and characterized. The crystal structures of complexes [Mn­(tolf-O)­(tolf-O,O′)­(phen)­(H<sub>2</sub>O)], [Mn<sub>2</sub>(μ<sub>2</sub>-tolf-O,O′)<sub>2</sub>(tolf-O,O′)<sub>2</sub>(bipyam)<sub>2</sub>], [Mn<sub>2</sub>(μ<sub>2</sub>-H<sub>2</sub>O)­(μ<sub>2</sub>-tolf-O,O′)<sub>2</sub>(tolf-O)<sub>2</sub>(py)<sub>4</sub>]·1.5MeOH·py, and [Mn­(μ<sub>2</sub>-tolf-O,O′)<sub>2</sub>(DMF)<sub>2</sub>]<sub><i>n</i></sub> have been determined by X-ray crystallography. The interaction of the complexes with serum albumin proteins was investigated, and relative high binding constant values were calculated. The ability of the compounds to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2′-azinobis­(3-ethylbenzothiazoline-6-sulfonic acid), and hydroxyl radicals was evaluated, and [Mn­(tolf)<sub>2</sub>(phen)­(H<sub>2</sub>O)] was the most active scavenger among the compounds. The compounds have also exhibited noteworthy <i>in vitro</i> inhibitory activity against soybean lipoxygenase. UV titration studies of the interaction of the complexes with calf-thymus (CT) DNA have proved the binding to CT DNA with [Mn­(μ<sub>2</sub>-tolf)<sub>2</sub>(DMF)<sub>2</sub>]<sub><i>n</i></sub> exhibiting the highest DNA-binding constant (<i>K</i><sub>b</sub> = 5.21 (±0.35) × 10<sup>5</sup> M<sup>–1</sup>). The complexes bind to CT DNA probably via intercalation as suggested by DNA-viscosity measurements and competitive studies with ethidium bromide (EB), which revealed the ability of the complexes to displace the DNA-bound EB.