Inorg. Chem. 2008, 47, 8736-8747
Copper-Hydroperoxo-Mediated N-Debenzylation Chemistry Mimicking Aspects of Copper Monooxygenases Debabrata Maiti, Amy A. Narducci Sarjeant, and Kenneth D. Karlin* Department of Chemistry, The Johns Hopkins UniVersity, Baltimore, Maryland 21218 Received April 5, 2008
A substantial oxidative N-debenzylation reaction along with PhCHdO formation occurs from a hydroperoxo-copper(II) complex that has a dibenzylamino substrate (sN(CH2Ph)2 appended as a substituent on one pyridyl group of its tripodal tetradentate TMPA (also TPA, (2-pyridylmethyl)amine)) ligand framework. During the course of the (LN(CH2Ph)2)CuII(-OOH) reactivity, the formation of a substrate and a -OOH-derived (an oxygen atom) alkoxo CuII(-OR) complex occurs. The observation that the same CuII(-OR) species occurs from CuΙ/PhIO chemistry suggests the possibility that a copper-oxo (cupryl) reactive intermediate forms during the alkoxo species formation; new ESI-MS data provide further support for this high-valent intermediate. A net H atom abstraction chemistry is proposed on the basis of the kinetic isotope effect studies provided here and the previously published study for a closely related CuII(-OOH) species incorporating dimethylamine (sN(CH3)2) as the internal substrate;27 the CuΙ/PhIO reactivity with similar isotope effect results provides further support. The reactivity of these chemical systems closely resembles the proposed oxidative N-dealkylation mechanisms that are effected by the copper monooxygenases, dopamine β-monooxygenase (DβM) and peptidylglycine-R-hydroxylating monooxygenase (PHM).
Introduction The study of copper(I)-dioxygen adducts and their (reduced) derivatives is of considerable current interest.1–8 In large part, these efforts comprise the desire to elucidate fundamental aspects such as the structural type along with associated spectroscopy, electronic structure, and, of course, reactivity patterns. Inspirations for such investigations also come from aspects of bioinorganic chemistry; we wish to provide fundamental information that may be relevant to copper metalloenzyme active sites, where the processing of molecular oxygen occurs. Included in the latter are the copper monooxygenases, peptidylglycine-R-hydroxylating monooxygenase (PHM) and dopamine β-monooxygenase (DβM), which are mammalian proteins that serve in the biosynthesis * To whom correspondence should be addressed. E-mail:
[email protected]. (1) Itoh, S.; Fukuzumi, S. Acc. Chem. Res. 2007, 40, 592–600. (2) Cramer, C.; Tolman, W. Acc. Chem. Res. 2007, 40, 601–608. (3) Suzuki, M. Acc. Chem. Res. 2007, 40, 609–617. (4) Itoh, S. Curr. Opin. Chem. Biol. 2006, 10, 115–122. (5) Quant Hatcher, L.; Karlin, K. D. J. Biol. Inorg. Chem. 2004, 9, 669– 683. (6) Mirica, L. M.; Ottenwaelder, X.; Stack, T. D. P. Chem. ReV. 2004, 104, 1013–1045. (7) Lewis, E. A.; Tolman, W. B. Chem. ReV. 2004, 104, 1047–1076. (8) Rolff, M.; Tuczek, F. Angew. Chem., Int. Ed. 2008, 47, 2344–2347.
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Figure 1. Homologus copper protein DβM (bottom), which transforms dopamine to norepinephrine, and homologous copper protein PHM (top), which hydroxylates the C-terminus of the peptide backbone, a process that is followed by N-dealkylation by PAL.
of various neuropeptides or hormones.9–12 Figure 1 outlines the specific reactions that are carried out. Each involves an (9) Klinman, J. P. J. Biol. Chem. 2006, 281, 3013–3016. (10) Bauman, A. T.; Yukl, E. T.; Alkevich, K.; McCormack, A. L.; Blackburn, N. J. J. Biol. Chem. 2006, 281, 4190–4198. (11) Chen, P.; Solomon, E. I. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 13105–13110. (12) Prigge, S. T.; Eipper, B.; Mains, R.; Amzel, L. M. Science 2004, 304, 864–867.
10.1021/ic800617m CCC: $40.75
2008 American Chemical Society Published on Web 09/11/2008
Copper-Hydroperoxo-Mediated N-Debenzylation Chemistry
insertion of one oxygen atom (from O2) into the substrate. For DβM, net benzylic hydroxylation occurs, whereas for PHM, hydroxylation is followed by N-dealkylation. The active sites of each enzyme are known to be very similar, and each contains two copper ions. Previous biophysical studies have shown these to be relatively far apart, and more recent X-ray crystallographic structures of PHM show them to be ∼11 Å apart.12 Thus, the mechanism of action focuses on the copper chemistry taking place at one of the two copper ions CuM (t CuB), whereas the other copper ion CuH (t CuA) serves to transfer electrons. Because of the history of biochemical/biophysical studies on these enzymes and in the context of considering various copper-dioxygen-derived species that are either known or unknown in inorganic chemistry, a hydroperoxo-copper(II) (CuII(-OOH)) complex and a superoxo-copper(II) (CuII(O2•-)) complex derived from the initial CuΙ-O2 chemistry or the high-valent cupryl [CuII-O•] have been discussed as species that might be responsible for an initial hydrogen atom abstraction reaction.2,4,8,9,11–18 For some time, a hydroperoxo complex was suggested, but more recently, both experimental and computational (bio)chemistry suggest that the CuII(O2•-) moiety is relevant.4,9–11,13 Furthermore, one crystal structure of PHM reveals what is best described as a CuMII(O2•-) moiety that is perfectly juxtaposed to the relevant substrate C-H bond. Other theoretical treatments prefer a prior (rather than subsequent) O-O cleavage from CuII(-OOH), which leads to a high-valent [Cu-O]2+ or [Cu-O]+ (equivalent to CuIII-O•) moiety (cupryl) that affects H atom transfer.14,15 To obtain answers or to provide insight, synthetic bioinorganic chemists have been actively pursuing the chemistry of mononuclear copper-dioxygen-derived complexes, especially in the reactivity toward substrates.2,19–27 Scheme 1 presents the several species that may affect H atom abstractions, which are followed (13) Chen, P.; Solomon, E. I. J. Am. Chem. Soc. 2004, 126, 4991–5000. (14) Yoshizawa, K.; Kihara, N.; Kamachi, T.; Shiota, Y. Inorg. Chem. 2006, 45, 3034–3041. (15) Crespo, A.; Marti, M. A.; Roitberg, A. E.; Amzel, L. M.; Estrin, D. A. J. Am. Chem. Soc. 2006, 128, 12817–12828. (16) Evans, J. P.; Ahn, K.; Klinman, J. P. J. Biol. Chem. 2003, 278, 49691– 49698. (17) Decker, A.; Solomon, E. I. Curr. Opin. Chem. Biol. 2005, 9, 152– 163. (18) Schro¨der, D.; Holthausen, M. C.; Schwarz, H. J. Phys. Chem. B 2004, 108, 14407–14416. (19) Fujii, T.; Yamaguchi, S.; Hirota, S.; Masuda, H. Dalton Trans. 2008, 164–170. (20) Kunishita, A.; Ishimaru, H.; Nakashima, S.; Ogura, T.; Itoh, S. J. Am. Chem. Soc. 2008, 130, 4244–4245. (21) Kunishita, A.; Teraoka, J.; Scanlon, J. D.; Matsumoto, T.; Suzuki, M.; Cramer, C. J.; Itoh, S. J. Am. Chem. Soc. 2007, 129, 7248–7249. (22) Hong, S.; Huber, S. M.; Gagliardi, L.; Cramer, C. C.; Tolman, W. B. J. Am. Chem. Soc. 2007, 129, 14190–14192. (23) Fujii, T.; Yamaguchi, S.; Funahashi, Y.; Ozawa, T.; Tosha, T.; Kitagawa, T.; Masuda, H. Chem. Commun. 2006, 4428–4430. (24) Maiti, D.; Lee, D.-H.; Gaoutchenova, K.; Wu¨rtele, C.; Holthausen, M. C.; Sarjeant, A. A. N.; Sundermeyer, J.; Schindler, S.; Karlin, K. D. Angew. Chem., Int. Ed. 2008, 47, 82–85. (25) Maiti, D.; Fry, H. C.; Woertink, J. S.; Vance, M. A.; Solomon, E. I.; Karlin, K. D. J. Am. Chem. Soc. 2007, 129, 264–265. (26) Maiti, D.; Lucas, H. R.; Narducci Sarjeant, A. A.; Karlin, K. D. J. Am. Chem. Soc. 2007, 129, 6998–6999. (27) Maiti, D.; Narducci Sarjeant, A. A.; Karlin, K. D. J. Am. Chem. Soc. 2007, 129, 6720–6721.
Scheme 1
by the net transfer of an oxygen atom to the substrate (i.e., monooxygenase activity). In biomimetic studies that are approached via coodination chemistry efforts, two types of hydroperoxide-copper species have been produced to date: µ-1,1-hydroperoxo-dicopper(II) complexes and mononuclear complexes. We have recently demonstrated substrate C-H activation chemistry starting from well-characterized dinuclear µ-(-OOH)-dicopper(II) complexes, oxidative N-dealkylation, or RCH2CtN oxidative cleavage (to the RCHdO aldehyde and cyanide).28,29 Suzuki has also observed a hydrocarbon attack from a CuII2(-OH)2 and H2O2 reaction, which gives a CuII-OORligand-substrate product.30 A number of well-characterized mononuclear CuII(-OOH) complexes have been described;31–37 however, substrate oxidations have been limited to organic sulfides37 or olefins (but in low yields).32 In our own laboratories, we have in the last year been able to demonstrate C-H activation and thus oxygenation from CuII(-OOH) complexes, as further discussed. There have been notable advances in the generation of a mononuclear CuII(O2•-) or CuIII(O22-) species,2,24,25,38 but a chemistry in which such entities attack substrate C-H bonds has yet to be described. There are no discrete examples or direct evidence of mononuclear high-valent copper-oxo species; however, see the further discussion below. Within the context of the introduction given above, we describe the chemistry of the new ligand LN(CH2Ph)2 (Chart 1, below) and its copper-complex-promoted oxidative chemistry. Whereas the main focus is on a mononuclear CuII(-OOH) species, [(LN(CH2Ph)2)CuII(-OOH)]+ (2), we complement it with (ligand)CuΙ-O2 reactivity and a separate attempt to interrogate the possible involvement of cupryl chemistry. (28) Li, L.; Narducci Sarjeant, A. A.; Karlin, K. D. Inorg. Chem. 2006, 45, 7160–7172. (29) Li, L.; Narducci Sarjeant, A. A.; Vance, M. A.; Zakharov, L. N.; Rheingold, A. L.; Solomon, E. I.; Karlin, K. D. J. Am. Chem. Soc. 2005, 127, 15360–15361. (30) Itoh, K.; Hayashi, H.; Furutachi, H.; Matsumoto, T.; Nagatomo, S.; Tosha, T.; Terada, S.; Fujinami, S.; Suzuki, M.; Kitagawa, T. J. Am. Chem. Soc. 2005, 127, 5212–5223. (31) Kodera, M.; Kita, T.; Miura, I.; Nakayama, N.; Kawata, T.; Kano, K.; Hirota, S. J. Am. Chem. Soc. 2001, 123, 7715–7716. (32) Ohta, T.; Tachiyama, T.; Yoshizawa, K.; Yamabe, T.; Uchida, T.; Kitagawa, T. Inorg. Chem. 2000, 39, 4358–4369. (33) Wada, A.; Harata, M.; Hasegawa, K.; Jitsukawa, K.; Masuda, H.; Mukai, M.; Kitagawa, T.; Einaga, H. Angew. Chem., Int. Ed. 1998, 37, 798–799. (34) Yamaguchi, S.; Wada, A.; Nagatomo, S.; Kitagawa, T.; Jitsukawa, K.; Masuda, H. Chem. Lett. 2004, 33, 1556–1557. (35) Yamaguchi, S.; Nagatomo, S.; Kitagawa, T.; Funahashi, Y.; Ozawa, T.; Jitsukawa, K.; Masuda, H. Inorg. Chem. 2003, 42, 6968–6970. (36) Yamaguchi, S.; Masuda, H. Sci. Technol. AdV. Mater. 2005, 6, 34– 47. (37) Fujii, T.; Naito, A.; Yamaguchi, S.; Wada, A.; Funahashi, Y.; Jitsukawa, K.; Nagatomo, S.; Kitagawa, T.; Masuda, H. Chem. Commun. 2003, 2700–2701. (38) Wu¨rtele, C.; Gaoutchenova, E.; Harms, K.; Holthausen, M. C.; Sundermeyer, J.; Schindler, S. Angew. Chem., Int. Ed. 2006, 45, 3867– 3869.
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Maiti et al. This work follows our recent work in which we employed a close analog [(LN(CH3)2)CuII(-OOH)]+ (3), where both ligands are the derivatives of TMPA (also TPA, tris(2-pyridylmethyl)amine)) (Chart 1, below); this shows that the hydroperoxo group that is coordinated to copper(II) can affect oxidative N-dealkylation chemistry on the juxtaposed dimethylamino substrate.27 In this Article, the chemistry of the LN(CH2Ph)2 analog is fully described. Experimental Section Materials and Methods. Unless otherwise stated, all solvents and chemicals used were commercially available analytical grade. Acetone, diethyl ether, pentane, propionitrile, methanol, and tetrahydrofuran (THF) were used after being passed through a 60cm-long column of activated alumina (Innovative Technologies) under argon. The deoxygenation of solvents was affected either by repeated freeze/pump/thaw cycles or by bubbling with argon for 30-45 min. Dioxygen was dried by being passed through a short column of supported P4O10 (Aquasorb, Mallinckrodt). The preparation and handling of air-sensitive compounds were performed under an argon atmosphere and by the use of standard Schlenk techniques or in an MBraun Labmaster 130 inert-atmosphere (
