pubs.acs.org/IC Published on Web 06/16/2010 r 2010 American Chemical Society Inorg. Chem. 2010, 49, 6399–6401 6399 DOI: 10.1021/ic100945n Reversible Apical Coordination of Imidazole between the Ni(III) and Ni(II) Oxidation States of a Dithiolate Complex: A Process Related to the Ni Superoxide Dismutase Marcello Gennari, † Maylis Orio, ‡ Jacques P  ecaut, § Frank Neese, ‡ Marie-No € elle Collomb, † and Carole Duboc* ,† † Universit e Joseph Fourier Grenoble 1/CNRS, D epartement de Chimie Mol  eculaire, UMR-5250, 38041 Grenoble Cedex 9 France, ‡ Institute for Physical and Theoretical Chemistry Universit € at Bonn, Wegelerstrasse 12, D-53113 Bonn, Germany, and § Laboratoire de Reconnaissance Ionique et Chimie de Coordination, UMR-E 3 CEA-UJF, 38054 Grenoble Cedex 09, France Received May 12, 2010 A bisamine aliphatic dithiolate [Ni II N 2 S 2 ] complex that does yield a metal-based oxidation has been synthesized. A square pyramidal [Ni III N 3 S 2 ] þ complex is generated by electrochemical oxidation in the presence of imidazole, mimicking the redox structural changes of NiSOD. In addition, EPR measurements coupled to DFT calculations demonstrate that the metal character in the redox active orbital increases drastically upon imidazole binding, impli- cating that these geometrical modifications are crucial for the stabilization of the Ni III state. Superoxide dismutases (SODs) serve a key antioxidant role in the protection of living cells against oxidative damage caused by the superoxide radical anion (O 2 •- ). This highly reactive oxygen species is destroyed by the SODs via dis- proportionation into hydrogen peroxide and molecular dioxygen. 1 Nickel-containing superoxide dimutases (NiSODs) are the most recently discovered SODs. 2 During catalysis, the Ni ion cycles between the þII and þIII oxidation states. 3 In the reduced state, the Ni II center is in a square planar [N 2 S 2 ] 3- environment with two thiolates from cysteines, one N-amidate from the peptide backbone, and the N-terminal amino group. 4,5 Upon oxidation, the Ni site is converted to a [N 3 S 2 ] square pyramid via the coordination of an axial N-imidazole ligand derived from a histidine. This unusual redox-state-dependent change in metal coordination number is crucial for SOD activity since mutations of the axial histidine lead to a drastic decrease of the enzyme reactivity. 6 It has been shown that synthetic square planar bisamide aliphatic dithiolate [Ni III N 2 S 2 ] - model complexes can gene- rate square pyramidal Ni III compounds via the axial coordi- nation of a pyridine ligand in the presence of a large excess of pyridine. 7-10 Nevertheless, neither the reversibility of this process nor the role of this apical coordination on the electronic structure of the Ni ion has been investigated in detail. Another unique feature of the NiSOD active site is the amide/amine coordination motif. Its role in the catalytic mechanism is to protect the thiolate ligands against oxidative damage 7 by ensuring a Ni-based oxidation process. 11-13 It was commonly admitted that synthetic bisamine [Ni II N 2 S 2 ] complexes have a propensity to undergo oxidation at the thiolate ligands and not at the Ni center, 14-16 in contrast to bisamide or monoanionic compounds. 7-10 Here, we report on the first bisamine dithiolate [Ni II N 2 S 2 ] complex that does yield a metal-based oxidation. Even more interestingly, an electrochemical investigation shows the reversible, oxidation- state-dependent generation of a square pyramidal [Ni III N 3 S 2 ] þ complex in the presence of imidazole. In addition, EPR mea- surements coupled to DFT calculations demonstrate that the nickel character in the redox active orbital increases drasti- cally upon imidazole binding. Finally, although this diamine Ni II complex does not mimic the mixed amide/amine co- ordination sphere of the NiSOD, it replicates some of its structural, dynamic, and redox properties. *To whom correspondence should be addressed. E-mail: carole.duboc@ ujf-grenoble.fr. (1) Miller, A. F. Curr. Opin. Chem. Biol. 2004, 8, 162–168. (2) Youn, H.-D.; Kim, E.-J.; Roe, J.-H.; Hah, Y. C.; Kang, S.-O. Biochem. J. 1996, 318, 889–896. (3) Choudhury, S. B.; Lee, J. W.; Davidson, G.; Yim, Y. I.; Bose, K.; Sharma, M. L.; Kang, S. O.; Cabelli, D. E.; Maroney, M. J. Biochemistry 1999, 38, 3744–3752. (4) Barondeau, D. P.; Kassmann, C. J.; Bruns, C. K.; Tainer, J. A.; Getzoff, E. D. Biochemistry 2004, 43, 8038–8047. (5) Wuerges, J.; Lee, J.-W.; Yim, Y.-I.; Yim, H.-S.; Kang, S.-O.; Djinovic Carugo, K. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 8569–8574. (6) Bryngelson, P. A.; Arobo, S. E.; Pinkham, J. L.; Cabelli, D. E.; Maroney, M. J. J. Am. Chem. Soc. 2004, 126, 460–461. (7) Fiedler, A. T.; Bryngelson, P. A.; Maroney, M. J.; Brunold, T. C. J. Am. Chem. Soc. 2005, 127, 5449–5462. (8) Kruger, H. J.; Holm, R. H. Inorg. Chem. 1987, 26, 3645–3647. (9) Kruger, H. J.; Peng, G.; Holm, R. H. Inorg. Chem. 1991, 30, 734–742. (10) Hanss, J.; Kruger, H. J. Angew. Chem., Int. Ed. 1998, 37, 360–363. (11) Shearer, J.; Zhao, N. Inorg. Chem. 2006, 45, 9637–9639. (12) Shearer, J.; Dehestani, A.; Abanda, F. Inorg. Chem. 2008, 47, 2649– 2660. (13) Mullins, C. S.; Grapperhaus, C. A.; Kozlowski, P. M. J. Biol. Inorg. Chem. 2006, 11, 617–625. (14) Mills, D. K.; Reibenspies, J. H.; Darensbourg, M. Y. Inorg. Chem. 1990, 29, 4364–4366. (15) Colpas, G. J.; Kumar, M.; Day, R. O.; Maroney, M. J. Inorg. Chem. 1990, 29, 4779–4788. (16) Grapperhaus, C. A.; Maguire, M. J.; Tuntulani, T.; Darensbourg, M. Y. Inorg. Chem. 1997, 36, 1860–1866.