Corroborative models of the cobalt(II) inhibited Fe/Mn superoxide dismutases.
Attempting to model superoxide dismutase (SOD) enzymes, we designed two new N3O-donor ligands to provide the same set of donor atoms observed in the active site of these enzymes: K(i)Pr2TCMA (potassium 1,4-diisopropyl-1,4,7-triazacyclononane-N-acetate) and KBPZG (potassium N,N-bis(3,5-dimethylpyrazolylmethyl) glycinate). Five new Co(II) complexes (1-5) were obtained and characterized by X-ray crystallography, mass spectrometry, electrochemistry, magnetochemistry, UV-vis, and electron paramagnetic resonance (EPR) spectroscopies. The crystal structures of 1 and 3-5 revealed five-coordinate complexes, whereas complex 2 is six-coordinate. The EPR data of complexes 3 and 4 agree with those of the Co(II)-substituted SOD, which strongly support the proposition that the active site of the enzyme structurally resembles these models. The redox behavior of complexes 1-5 clearly demonstrates the stabilization of the Co(II) 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 1 and 3-5 that probably changes from a trigonal bipyramidal (high spin, d7) to octahedral (low spin, d6) as Co(II) is oxidized to Co(III), which is also expected to be accompanied by a spin-state conversion. As the redox potentials to convert the Co(II) to Co(III) are high, it can be inferred that the redox potential of the Co(II)-substituted SOD may be outside the range required to convert the superoxide radical (O2*-) 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(II)-substituted SOD.
Scarpellini
Marciela
M
Willard H. Dow Laboratories, Department of Chemistry, University of Michigan, 930 North University, Ann Arbor, Michigan 48108, USA.
Wu
Amy J
AJ
Kampf
Jeff W
JW
Pecoraro
Vincent L
VL
D001665:Binding Sites; D002412:Cations; D003035:Cobalt / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D004579:Electron Transport; D006861:Hydrogen Peroxide / Q000737:chemistry; D007501:Iron / Q000737:chemistry*; D008024:Ligands; D008345:Manganese / Q000737:chemistry*; D008667:Metalloproteins / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013057:Spectrum Analysis; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000737:chemistry*
D002412:Cations; D008024:Ligands; D008667:Metalloproteins; D003035:Cobalt; D008345:Manganese; D006861:Hydrogen Peroxide; D007501:Iron; D013482:Superoxide Dismutase