Dioxygen Reactivity of Fully Reduced [LFe II ‚‚‚Cu I ] + Complexes Utilizing Tethered Tetraarylporphyrinates: Active Site Models for Heme-Copper Oxidases Telvin D. Ju, † Reza A. Ghiladi, † Dong-Heon Lee, † Gino P. F. van Strijdonck, † Amina S. Woods, ‡ Robert J. Cotter, ‡ Victor G. Young Jr., § and Kenneth D. Karlin* ,† Department of Chemistry, The Johns Hopkins University, Charles and 34th Streets, Baltimore, Maryland 21218, Department of Pharmacology and Molecular Sciences, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, and Department of Chemistry, The University of Minnesota, Minneapolis, Minnesota 55455 ReceiVed January 6, 1999 In aerobic organisms, the heme a 3 -Cu B binuclear active center in heme-copper oxidases is responsible for O 2 binding, O-O reductive cleavage, and protonation to give H 2 O. 1 The enzyme couples this 4e - /4H + O 2 reduction to the translocation of protons, creating the membrane potential used to drive ATP synthesis. There is considerable interest in developing structural, spectro- scopic, and functional active site models, 2-4 but only a few discrete heterobinuclear Fe II ‚‚‚Cu I species have been well char- acterized and employed for critical O 2 -reactivity studies. 3,5-8 We wish to study systems where the (porphyrinate)Fe II /LCu I / O 2 chemistry (L ) copper ligand) may be controlled (but also systematically varied), in situations where intramolecular reactions are favored. Here, we report such chemistry with heterobinucle- ating ligands, the constitutional isomers 6 L and 5 L, where a tetradentate TMPA 9 ligating moiety is covalently attached to the periphery of a porphryin, through either the 6-position ( 6 L) or the 5-position ( 5 L) of one pyridine arm (Scheme 1). 6 L and 5 L take advantage by employing a Cu ligand with an established (TMPA)Cu I /O 2 chemistry with known kinetics, thermodynamics, structures, and spectroscopy. 10 In addition to the description of new Fe II (with “empty tether”) and Fe II ‚‚‚Cu I complexes with 6 L and 5 L, we report biomimetic reactions where μ-oxo Fe III -O- Cu II cores are generated directly from O 2 reduction; 11 a crystal structure of the 6 L oxygenation product is described. The complexes described herein (Scheme 1) are characterized by multinuclear NMR 12 and UV-visible spectroscopies, and supported by MALDI-TOF mass spectrometry on isolated solids. 13 Metalation begins with addition of excess FeCl 2 to either the 6 L or 5 L ligands, followed by air oxidation. This procedure yields † The Johns Hopkins University. ‡ The Johns Hopkins School of Medicine. § The University of Minnesota. (1) (a) Ferguson-Miller, S.; Babcock, G. T. Chem. ReV. 1996, 96, 2889- 2907. (b) Ostermeier, C.; Harrenga, A.; Ermler, U.; Michel, H. Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 10547-10553. (c) Yoshikawa, S.; Shinzawa-Itoh, K.; Nakashima, R.; Yaono, R.; Yamashita, E.; Inoue, N.; Yao, M.; Jei-Fei, M.; Libeu, C. P.; Mizushima, T.; Yamaguchi, H.; Tomizaki, T.; Tsukihara, T. Science 1998, 280, 1723-1729. (2) (a) Kitajima, N. AdV. Inorg. Chem. 1992, 39,1-77. (b) Holm, R. H. Pure Appl. Chem. 1995, 67, 217-224. (c) Karlin, K. D.; Lee, D.-H.; Obias, H. V.; Humphreys, K. J. Pure Appl. Chem. 1998, 70, 855-862. (3) Collman, J. P. Inorg. Chem. 1997, 36, 5145-5155. (4) (a) Obias, H. V.; van Strijdonck, G. P. F.; Lee, D.-H.; Ralle, M.; Blackburn, N. J.; Karlin, K. D. J. Am. Chem. Soc. 1998, 120, 9696- 9697. (b) Kopf, M.-A.; Karlin, K. D. In Biomimetic Oxidations; Meunier, B., Ed.; Imperial College Press: London, 1999; Chapter 7, in press. (c) Nanthakumar, A.; Fox, S.; Karlin, K. D. J. Chem. Soc., Chem. Commun. 1995, 499-501. (5) Berry, K. J.; Gunter, M. J.; Murray, K. S. In Oxygen and Life; The Royal Society of Chemistry: London, U.K., 1980; Vol. Special Publication No. 39; pp 170-179. (6) Collman, J. P.; Rapta, M.; Bro ¨ring, M.; Raptova, L.; Schwenninger, R.; Boitrel, B.; Fu, L.; L’Her, M. J. Am. Chem. Soc. 1999, 121, 1387- 1388 and references cited therein. (7) Monzani, E.; Casella, L.; Gullotti, M.; Panigada, N.; Franceschi, F.; Papaefthymiou, V. J. Mol. Catal. A: Chem. 1997, 117, 199-204. (8) Sasaki, T.; Nakamura, N.; Naruta, Y. Chem. Lett. 1998, 351-352. (9) Abbreviations used: TMPA, tris(2-pyridylmethyl)amine; F8-TPP, tetrakis- (2,6-difluorophenyl)porphyrinate; MALDI-TOF-MS, matrix-assisted laser desorption ionization time-of-flight mass spectrometry; BAr F , tetrakis- (3,5-bis(trifluoromethyl)phenyl)borate; THF, tetrahydrofuran; EXAFS, extended X-ray absorption fine structure. (10) (a) Tyekla ´r, Z.; Jacobson, R. R.; Wei, N.; Murthy, N. N.; Zubieta, J.; Karlin, K. D. J. Am. Chem. Soc. 1993, 115, 2677-2689. (b) Karlin, K. D.; Kaderli, S.; Zuberbu ¨hler, A. D. Acc. Chem. Res. 1997, 30, 139- 147. (c) Karlin, K. D.; Zuberbu ¨hler, A. D. In Bioinorganic Catalysis: Second Edition, ReVised and Expanded; Reedijk, J., Bouwman, E., Eds.; Marcel Dekker: New York, 1999; pp 469-534. (11) (a) With separate mononuclear reduced heme and copper(I) complexes, we have previously 11b,c described details of the reaction of (F8-TPP)Fe II plus [(TMPA)Cu I (RCN)] + with O2, which produces the μ-oxo complex [(F8-TPP)Fe III -O-Cu II (TMPA)] + (5). Isotope labeling showed that the oxo atom in 5 is derived from O2, and the reaction stoichiometry (unpublished results) is Fe:Cu:O2 ) 2:2:1. (b) Karlin, K. D.; Nantha- kumar, A.; Fox, S.; Murthy, N. N.; Ravi, N.; Huynh, B. H.; Orosz, R. D.; Day, E. P. J. Am. Chem. Soc. 1994, 116, 4753-4763. (c) Nanthakumar, A.; Nasir, M. S.; Karlin, K. D.; Ravi, N.; Huynh, B. H. J. Am. Chem. Soc. 1992, 114, 6564-6566. (12) 1 H NMR spectra, particularly pyrrole resonances, are useful as a criterion for compound purity, since most of the compounds (including impurities) possess paramagnetically shifted and distinctive (i.e., highly sensitive to spin and oxidation states) resonances. (13) See Supporting Information. Scheme 1 2244 Inorg. Chem. 1999, 38, 2244-2245 10.1021/ic9900511 CCC: $18.00 © 1999 American Chemical Society Published on Web 04/24/1999