Seven-Coordinate Iron and Manganese Complexes with Acyclic and Rigid Pentadentate Chelates and Their Superoxide Dismutase Activity

The reactions of seven-coordinate [Fe^III(dapsox)(H₂O)₂]ClO₄·H₂O (1), [Fe^II(H₂dapsox)(H₂O)₂](NO₃)₂·H₂O (2), and [Mn^II(H₂dapsox)(CH₃OH)(H₂O)](ClO₄)₂(H₂O) (3) complexes of the acyclic and rigid pentadentate H₂dapsox ligand [H₂dapsox = 2,6-diacetylpyridinebis(semioxamazide)] with superoxide have been studied spectrophotometrically, electrochemically, and by a submillisecond mixing UV/vis stopped-flow in dimethyl sulfoxide (DMSO). The same studies were performed on the seven-coordinate [Mn^II(Me₂[15]pyridinaneN₅)(H₂O)₂]Cl₂·H₂O (4) complex with the flexible macrocyclic Me₂[15]pyridinaneN₅ ligand (Me₂[15]pyridinaneN₅ = trans-2,13-dimethyl-3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),14,16-triene), which belongs to the class of proven superoxide dismutase (SOD) mimetics. The X-ray crystal structures of 2−4 were determined. All complexes possess pentagonal-bipyramidal geometry with the pentadentate ligand in the equatorial plane and solvent molecules in the axial positions. The stopped-flow experiments in DMSO (0.06% of water) reveal that all four metal complexes catalyze the fast disproportionation of superoxide under the applied experimental conditions, and the catalytic rate constants are found to be (3.7 ± 0.5) × 10⁶, (3.9 ± 0.5) × 10⁶, (1.2 ± 0.3) × 10⁷, and (5.3 ± 0.8) × 10⁶ M^-1 s^-1 for 1−4, respectively. The cytochrome c McCord−Fridovich (McCF) assay in an aqueous solution at pH = 7.8 resulted in the IC₅₀ values (and corresponding k_McCF constants) for 3 and 4, 0.013 ± 0.001 μM (1.9 ± 0.2 × 10⁸ M^-1 s^-1) and 0.024 ± 0.001 μM (1.1 ± 0.3 × 10⁸ M^-1 s^-1), respectively. IC₅₀ values from a nitroblue tetrazolium assay are found to be 6.45 ± 0.02 and 1.36 ± 0.03 μM for 1 and 4, respectively. The data have been compared with those obtained by direct stopped-flow measurements and discussed in terms of the side reactions that occur under the conditions of indirect assays.