Corroborative Models of the Cobalt(II) Inhibited Fe/Mn Superoxide Dismutases

Attempting to model superoxide dismutase (SOD) enzymes, we designed two new N<sub>3</sub>O-donor ligands to provide the same set of donor atoms observed in the active site of these enzymes:  K<sup><i>i</i></sup>Pr<sub>2</sub>TCMA (potassium 1,4-diisopropyl-1,4,7-triazacyclononane-<i>N</i>-acetate) and KBPZG (potassium <i>N</i>,<i>N</i>-bis(3,5-dimethylpyrazolylmethyl) glycinate). Five new Co<sup>II</sup> complexes (<b>1</b>−<b>5</b>) were obtained and characterized by X-ray crystallography, mass spectrometry, electrochemistry, magnetochemistry, UV−vis, and electron paramagnetic resonance (EPR) spectroscopies. The crystal structures of <b>1</b> and <b>3</b>−<b>5</b> revealed five-coordinate complexes, whereas complex <b>2</b> is six-coordinate. The EPR data of complexes <b>3</b> and <b>4</b> agree with those of the Co<sup>II</sup>-substituted SOD, which strongly support the proposition that the active site of the enzyme structurally resembles these models. The redox behavior of complexes <b>1</b>−<b>5</b> clearly demonstrates the stabilization of the Co<sup>II</sup> state in the ligand field provided by these ligands. The irreversibility displayed by all of the complexes is probably related to an electron-transfer process followed by a rearrangement of the geometry around the metal center for complexes <b>1</b> and <b>3</b>−<b>5</b> that probably changes from a trigonal bipyramidal (high spin, d<sup>7</sup>) to octahedral (low spin, d<sup>6</sup>) as Co<sup>II</sup> is oxidized to Co<sup>III</sup>, which is also expected to be accompanied by a spin-state conversion. As the redox potentials to convert the Co<sup>II</sup> to Co<sup>III</sup> are high, it can be inferred that the redox potential of the Co<sup>II</sup>-substituted SOD may be outside the range required to convert the superoxide radical (O<sub>2</sub><sup>•-</sup>) to hydrogen peroxide, and this is sufficient to explain the inactivity of the enzyme. Finally, the complexes reported here are the first corroborative structural models of the Co<sup>II</sup>-substituted SOD.