Built-in Axial Base Binding on Phenanthroline-Strapped Zinc(II) and Iron(III) Porphyrins Fre ´de ´ ric Melin, † Sylvie Choua,* ,‡ Maxime Bernard, ‡ Philippe Turek, ‡ and Jean Weiss* ,† Chimie des Ligands a ` Architecture Contro ˆ le ´ e, LC3 CNRS-ULP, Institut Le Bel, 4 rue Blaise Pascal, 67070 Strasbourg Cedex, France, and Synthe ` se et Proprie ´ te ´ s Optiques et Magne ´ tiques de Mate ´ riaux Mole ´ culaires et Macromole ´ culaires, Institut Charles Sadron, CNRS-UPR 22, 6 rue Boussingault, BP 40016, 67083 Strasbourg Cedex, France Received June 20, 2006 In addition to the need for functional models of cytochrome c oxidase, structural models are still required for a better understanding of the small reorganizations occurring during the catalytic cycle. An efficient synthetic approach has been designed to prepare several phenanthroline-strapped porphyrins, two of them bearing two pendant imidazoles. These built-in bases are both potentially able to act as axial bases for the metalloporphyrin and as complementary ligands for copper if necessary. Diamagnetic zinc(II) was used to demonstrate that the distal/ proximal selectivity demonstrated by exogenic bases binding studies can be extended to the coordination of iron- (III). Combination of EPR and paramagnetic 1 H NMR shows that the imidazole binding on the zinc species can be further extended to the iron(III) species in dilute conditions. Introduction Cytochrome c oxidase is the terminal enzyme of the mitochondrial respiratory chain and catalyzes the four electron reduction of dioxygen into water at low overpoten- tials without the formation of partial reduction byproducts. 1 The active site comprises a heme (a3) associated with a copper(I) center (CuB) coordinated by three histidine moi- eties, one of which is linked to a tyrosine. It has been proposed that this tyrosine residue plays a key role in the enzyme function, possibly as a relay in proton or electron transfer or as a structuring component in the environment of CuB. 2 While early functional models of cytochrome c oxidase were based exclusively on the reproduction of the coordination sphere of each metal in the binuclear complex, 3 a new generation of models is now emerging that incorporate a tyrosine residue cross-linked to one of the imidazoles surrounding the CuB center. 4 Despite many efforts, the elucidation of CcO’s catalytic mechanism still requires both structural and functional models of the active site and eventual isolation of postulated intermediates 5 for comparison with “natural” spectroscopic data. Toward this goal, the high availability of a phenanthroline-strapped porphyrin denomi- nated porphen (Chart 1) 6 and its ability to form bimetallic complexes 7 has prompted us to investigate its derivatization to introduce built-in imidazoles as both axial base and auxiliary copper ligand. In these ligands, the rigid character of the phenanthroline binding site may allow the stabilization of bridged Cu-Fe intermediates. We report hereafter the synthesis of two promising candidates for cytochrome c oxidase models that are represented in Chart 1. Only one of the imidazole moieties acts as an axial base in zinc-metalated * To whom correspondence should be addressed. E-mail: jweiss@ chimie.u-strasbg.fr (J.W.). † Institut Le Bel. ‡ Institut Charles Sadron. (1) Fergusson-Miller, S.; Babcock, G. T. Chem. ReV. 1996, 96, 2889. (2) Proshlyakov, D. A.; Pressler, M. A.; DeMaso, C.; Leykam, J. F.; DeWitt, D. L.; Babcock, G. T. Science 2000, 290, 1588 and references therein. (3) (a) Collman, J. P.; Boulatov, R.; Sunderland, C. J.; Fu, L. Chem. ReV. 2004, 104, 561 and references cited. (b) Kim, E.; Chufan, E. E.; Kamaraj, K.; Karlin, K. D. Chem. ReV. 2004, 104, 1077 and references cited. (c) Naruta, Y.; Sasaki, T.; Tani, F.; Tachi, Y.; Kawato, N.; Nakamura, N. J. Inorg. Biochem. 2001, 83, 239 and references cited. (4) (a) Liu, J.-G.; Naruta, Y.; Tani, F. Angew. Chem., Int. Ed. 2005, 44, 1836. (b) del Rı ´o, D.; Sarangi, R.; Chufa ´n, E. E.; Karlin, K. D.; Hedman, B.; Hodgson, K. O.; Solomon, E. I. J. Am. Chem. Soc. 2005, 127, 11969. (c) Kim, E.; Kamaraj, K.; Galliker, B.; Rubie, N. D.; Moe ¨nne-Loccoz, P.; Kaderli, S.; Zuberbu ¨hler, A. D.; Karlin, K. D. Inorg. Chem. 2005, 44, 1238. (d) Collman, J. P.; Decre ´au, R. A.; Zhang, C. J. Org. Chem. 2004, 69, 3546. (e) Liu, J.-G.; Naruta, Y.; Tani, F.; Chisiro, T.; Tachi, Y. Chem. Commun. 2004, 120. (5) Blomberg, M. R. A.; Siegbahn, P. E.; Wikstro ¨m, M. Inorg. Chem. 2003, 42, 5231. (6) Wytko, J. A.; Graf, E.; Weiss, J. J. Org. Chem. 1992, 57, 1015. (7) Giraudeau, A.; Gisselbrecht, J.-P.; Gross, M.; Weiss, J. J. Chem. Soc., Chem. Commun. 1993, 1103. Inorg. Chem. 2006, 45, 10750-10757 10750 Inorganic Chemistry, Vol. 45, No. 26, 2006 10.1021/ic0611185 CCC: $33.50 © 2006 American Chemical Society Published on Web 11/18/2006