An Iron-Peroxo Porphyrin Complex: New Synthesis and Reactivity Toward a Cu(II) Complex Giving a Heme-Peroxo-Copper Adduct

Article abstract of DOI:10.1021/ja036632d

Side-on η²-peroxo-iron porphyrins are strong nucleophiles. In cytochrome P450-like aromatase and other enzymes, such species are postulated as the active oxidants. In cytochrome c oxidase, heme_a3-peroxo, heme_a3-hydroperoxo, or heme_a3-(μ-peroxo)-copper species are proposed as transient intermediates forming prior to O-O bond cleavage. In this report, we describe (1) a facile method for reduction of a heme-O₂ species [(F₈TPP)Fe^III(O₂^-)(S)] (2), generating the ferric peroxo porphyrin complex [(F₈TPP)Fe^III(O₂^2-)]^- (3) (UV-vis, THF: λ_max = 435 (Soret), 540(sh), 561; EPR: g = 8.7, 4.2), and (2) that this can be subsequently reacted with a ligand-copper(II) complex, [Cu^II(TMPA)-(CH₃CN)](ClO₄)₂ (4), affording a heme-peroxo-copper heterobinuclear compound, [(F₈TPP)Fe^II(O₂^2-)-Cu^II(TMPA)](ClO₄) (5). Generation of [(F₈TPP)Fe^III(O₂^2-)]^- (3) using cobaltocene as a one-electron reductant was monitored by UV-vis, EPR, and ¹H NMR spectroscopies. Reaction between 3 and 4 was followed by UV-vis spectroscopy, and the product 5 could be precipitated and characterized. Coordination by copper(II) in 5 makes possible further reduction of the μ-peroxo complex by cobaltocene yielding the μ-oxo analogue, [(F₈TPP)Fe^III(O^2-)-Cu^II(TMPA)](ClO₄) (6). Copyright

Full text of DOI:10.1021/ja036632d

Published on Web 12/09/2003
An Iron-Peroxo Porphyrin Complex: New Synthesis and Reactivity Toward a
Cu(II) Complex Giving a Heme-Peroxo-Copper Adduct
Eduardo E. Chufa´n and Kenneth D. Karlin*
Department of Chemistry, The Johns Hopkins UniVersity, Charles and 34th Streets, Baltimore, Maryland 21218
Received June 11, 2003; E-mail: karlin@jhu.edu
Ferric peroxo porphyrin complexes
are strong nucleophiles capable of epoxidizing electron-deficient
olefins.1,2 Such species are postulated as the active oxidant in the
cytochrome P450-like aromatase and other enzymes.2 [(P)FeIII(O22-)]-
complexes3 were first synthesized by Valentine and co-workers,
from reaction of [(P)FeIII-Cl] with potassium superoxide in aprotic
solvents.4-8 The side-on η2-peroxo high-spin ferric formulation is
based on physical-spectroscopic studies,9,10 and by analogy to the
structurally characterized η2-peroxomanganese complex [(TPP)Mn-
Figure 1. UV-vis spectra of (F8TPP)FeII(THF)2 (1), (F8TPP)FeIII(O2-)(THF)
(O22-)]-.11,12
(2) and [CoIIICp2][(F8TPP)FeIII(O22-)]- (3) in THF at 193 K. See text for
In cytochrome c oxidase (CcO), hemea3-peroxo, hemea3-
hydroperoxo or hemea3-(µ-peroxo)-copper13 species are likely
transients which form following electron transfer from the proximal
Cu1+B site to the initially generated hemea3-O2 adduct (formally a
superoxo-iron(III) species).14 Thus, a viable approach to the
understanding of O2-binding and reductive O-O cleavage at the
CcO heme‚‚‚Cu active site is to probe reactions between iron-
peroxo hemea3 synthetic models and CuB-site analogue complexes.
In this report, we describe (Scheme 1) (1) a facile method for
reduction of a heme-O2 species [(F8TPP)FeIII(O2-)(S)] (2),3
generating the ferric peroxo porphyrin complex [(F8TPP)FeIII(O22-)]-
(3) and (2) that this can be subsequently reacted with a ligand-
copper(II) complex, affording a heme-peroxo-copper heterobi-
nuclear compound. This distinctive approach to generating heme-
further discussion.
peroxo and heme-peroxo-copper complexes is of considerable
interest since these compounds closely resemble short-lived species
relevant to the cytochrome c oxidase reaction mechanism.14
Immediate formation of the iron(III)-superoxo complex [(F8TPP)-
FeIII(O2-)(THF)] (2) [λmax ) 416 (Soret) and 534 nm]15 is observed
upon bubbling a tetrahydrofuran (THF) solution of [(F8TPP)FeII-
(THF)2] (1) [λmax ) 422 (Soret) and 541 nm] with dioxygen at
-80 °C (Scheme 1 and Figure 1). After removal of excess O2 by
vacuum/Ar cycling, addition of 1 equiv of cobaltocene (as a strong
outer-sphere reductant)16,17 results in the generation of [CoIIICp2]-
[(F8TPP)FeIII(O22-)]- (3) based on its characteristic UV-vis
spectrum [λmax ) 435 (Soret), 540 (sh) and 561 nm].10,18 Similar
chemistry is observed with CH2Cl2/10% CH3CN (v/v) as solvent,
where CH3CN serves as an axial heme ligand promoting formation
of [(F8TPP)FeIII(O2-)(CH3CN)].15,17
Scheme 1
A number of lines of evidence further support the formulation
given for [CoIIICp2][(F8TPP)FeIII(O22-)]- (3):
(1) The presence of the cobaltocenium ([CoIIICp2]+) as the
countercation is evident by the occurrence of a characteristic new
UV band at 262 nm,19 and a 6.7 ppm signal in the 1H NMR
spectrum (CH2Cl2/10% CH3CN, -80 °C).16
(2) EPR spectra of [CoIIICp2][(F8TPP)FeIII(O22-)]- (3) (Figure
2) show a strong marker signal at g ) 4.2, typical for rhombic
[(P)FeIII(O22-)]- complexes10,18 and η2-peroxo-nonheme iron spe-
cies.20,21 With excess CoIICp2, which eliminates high-spin iron(III)
heme impurities (such as (F8TPP)Fe-OH, g ≈ 7.0), the additional
characteristic g ) 8.7 signal is also observed.10,20,21
(3) [(F8TPP)FeIII(O2-)(THF)] (2) is characterized by its typical
1H-NMR diamagnetic spectrum, (δpyrrole ) 8.5 ppm, THF-d8
solvent).15 Addition of CoIICp2 leads to a downfield shifting of the
pyrrole resonance to 90 ppm.17 The complex shows Curie behavior
(-80 to -40 °C) and extrapolation to room temperature leads to
an assignment of this signal occurring at 68 ppm for [CoIIICp2]-
[(F8TPP)FeIII(O22-)]- (3),17 close to published values for other
[(P)FeIII(O22-)]- complexes.22,23
9
16160
J. AM. CHEM. SOC. 2003, 125, 16160-16161
10.1021/ja036632d CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Institutes of Health (K.D.K., GM60353), CONICET-Argentina, and
Universidad Nac. de San Luis-Argentina (E.E.C.) for research
support.
Supporting Information Available: Synthetic and spectroscopic
(UV-vis and 1H-NMR) details, pp S1-S14, with Figures S1-S8
(PDF). This material is available free of charge via the Internet at http://
pubs.acs.org.
References
(1) Sisemore, M. F.; Burstyn, J. N.; Valentine, J. S. Angew. Chem., Int. Ed.
1996, 35, 206-208.
(2) Wertz, D. L.; Valentine, J. S. Struct. Bonding (Berlin) 2000, 97, 37-60.
(3) Abbreviations used: P ) porphyrinate; S ) solvent; F8TPP ) tetrakis-
(2,6-difluoro-phenyl)porphyrinate; TPP ) tetra(phenyl)porphyrinate; Cp
) cyclopentadienyl; TMPA ) tris(2-pyridyl-methyl)amine.
(4) McCandlish, E.; Miksztal, A. R.; Nappa, M.; Sprenger, A. Q.; Valentine,
J. S.; Stong, J. D.; Spiro, T. G. J. Am. Chem. Soc. 1980, 102, 4268-
4271.
Figure 2. X-band EPR spectra of [CoIIICp2][(F8TPP)FeIII(O22-)]- (3)
generated with 1 equiv of cobaltocene (upper spectrum) and with an excess
of cobaltocene (lower spectrum) in CH2Cl2/10% CH3CN: temperature, 5
K; time constant 20.48 ms; sweep width 6000 G.
(5) [(P)Fe(O2)]- can also be obtained either by electrochemical6 or chemical
[aluminum hydride reagent]7 reduction of a porphyrin ferrous dioxygen,
or by addition of dioxygen to an iron(I) porphyrin.8
(4) The peroxidic nature of 3 is demonstrated by its protonation
using hydrochloric acid, leading to the formation of (F8TPP)FeIII-
Cl and hydrogen peroxide (>70% yield).17,24
(6) Welborn, C. H.; Dolphin, D.; James, B. R. J. Am. Chem. Soc. 1981, 103,
2869-2871.
(7) Schappacher, M.; Weiss, R.; Montiel-Montoya, R.; Trautwein, A.; Tabard,
A. J. Am. Chem. Soc. 1985, 107, 3736-378.
The reaction of [CoIIICp2][(F8TPP)FeIII(O22-)]- (3) toward the
pentacoordinated copper(II) complex [CuII(TMPA)(CH3CN)](ClO4)2
(4)25,26 (which has a labile CH3CN ligand) is suggestive of
nucleophilic behavior of 3 (Scheme 1), otherwise known for
[(P)FeIII(O22-)]- complexes.1,2 When 4 was added to a solution of
3 generated in THF at -95 °C, heme-µ-peroxo-copper complex
[(F8TPP)FeIII-(O22-)-CuII(TMPA)](ClO4) (5) is obtained;17 a solid
form was isolated by precipitation with heptane.27 Redissolution
(-80 °C) showed that the solid retains the unique UV-vis and 1H
NMR spectroscopic features known for 5,17 which was previously
only generated by oxygenation of a 1:1 mixture of reduced
complexes (F8TPP)FeII and [CuI(TMPA)(CH3CN)](ClO4), Scheme
1.12,28-30
(8) Reed, C. A. In Electrochemical and Spectrochemical Studies of Biological
Redox Components; K. M. Kadish, Ed.; American Chemical Society:
Washington, DC, 1982; p 333.
(9) Friant, P.; Goulon, J.; Fischer, J.; Ricard, L.; Schappacher, M.; Weiss,
R.; Momenteau, M. NouV. J. Chim. 1985, 9, 33-40.
(10) Burstyn, J. N.; Roe, J. A.; Miksztal, A. R.; Shaevitz, B. A.; Lang, G.;
Valentine, J. S. J. Am. Chem. Soc. 1988, 110, 1382-1388.
(11) VanAtta, R. B.; Strouse, C. E.; Hanson, L. K.; Valentine, J. S. J. Am.
Chem. Soc. 1987, 109, 1425-1434.
(12) The structure of a heme-O2-Cu assembly with η2-peroxo-heme moiety
(and η1-ligation to Cu) has recently been described. See Chishiro, T.;
Shimazaki, Y.; Tani, F.; Tachi, Y.; Naruta, Y.; Karasawa, S.; Hayami,
S.; Maeda, Y. Angew. Chem., Int. Ed. 2003, 42, 2788-2791.
(13) 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.
(14) Proshlyakov, D. A.; Pressler, M. A.; Babcock, G. T. Proc. Natl. Acad.
Sci. U.S.A. 1998, 95, 8020-8025.
It is noteworthy that excess CoIICp2 (E° ≈ -1.3 V vs Fc+/Fc)16
does not react with the η2-peroxo complex [(F8TPP)FeIII(O22-)]-
(3); however, it does reduce the µ-peroxo complex [(F8TPP)FeIII-
(O22-)-CuII(TMPA)]+ (5) (CH3CN, -40 °C), yielding the corre-
sponding µ-oxo species [(F8TPP)FeIII-(O2-)-CuII(TMPA)]+ (6)
[UV-vis: λmax ) 433 (Soret) and 555 nm] (Scheme 1).28 This
inertness toward reductants has also been observed for the η2-peroxo
complex [(EDTA)FeIII(O22-)]3- and is indicative that the O-O bond
is not activated for reductive cleavage.20 The details of this peroxo-
to-oxo conversion (5 to 6) are unclear and require further study;
coordination by copper(II) as an electrophile in 5 probably assists
the O-O bond “activation”.
In summary, we have developed a rather simple method to
generate an important peroxo-heme species via O2 chemistry and
chemical reduction with cobaltocene. This peroxo-heme species
reacts with a copper(II) complex, yielding a heme-peroxo-copper
adduct which resembles a suggested transient in the reaction
mechanism of CcO.14 This reactivity methodology opens avenues
for future investigation whereby [CoIIICp2][(F8TPP)FeIII(O22-)]- (3)
can be reacted with copper(I) complexes (which can serve as both
a copper source and a reducing equivalent),29 and possibly additional
proton or electron sources,31 in an attempt to understand reductive
cleavage of an O-O bond in a heme-Cu environment.
(15) Ghiladi, R. A.; Kretzer, R. M.; Guzei, I.; Rheingold, A. L.; Neuhold, Y.-
M.; Hatwell, K. R.; Zuberbu¨hler, A. D.; Karlin, K. D. Inorg. Chem. 2001,
40, 5754-5767.
(16) Connelly, N. G.; Geiger, W. E. Chem. ReV. 1996, 96, 877-910.
(17) See Supporting Information.
(18) Selke, M.; Sisemore, M. F.; Valentine, J. S. J. Am. Chem. Soc. 1996,
118, 2008-2012.
(19) Sheats, J. E. J. Organomet. Chem. Libr. 1979, 7, 461-521.
(20) Neese, F.; Solomon, E. I. J. Am. Chem. Soc. 1998, 120, 12829-12848.
(21) Roelfes, G.; Vrajmasu, V.; Chen, K.; Ho, R. Y. N.; Rohde, J.-U.;
Zondervan, C.; la Crois, R. M.; Schudde, E. P.; Lutz, M.; Spek, A. L.;
Hage, R.; Feringa, B. L.; Muenck, E.; Que, L., Jr. Inorg. Chem. 2003,
42, 2639-2653.
(22) Shirazi, A.; Goff, H. M. J. Am. Chem. Soc. 1982, 104, 6318-6322.
(23) Selke, M.; Valentine, J. S. J. Am. Chem. Soc. 1998, 120, 2652-2653.
(24) Vibrational spectroscopic characterization of peroxide 3 has been thwarted
by its thermal instability (IR) or photodecomposition (resonance Raman).
(25) Fox, S.; Nanthakumar, A.; Wikstro¨m, M.; Karlin, K. D.; Blackburn, N. J.
J. Am. Chem. Soc. 1996, 118, 24-34.
(26) While we have observed no problems, perchlorate salts are potentially
explosive and should be handled with great care.
(27) [CoIIICp2](ClO4) also coprecipitates, as evidenced by a 262-nm UV
absorption19 and 5.6-ppm signal in the 1H NMR spectrum.16
(28) Ghiladi, R. A.; Hatwell, K. R.; Karlin, K. D.; Huang, H.-w.; Moeenne-
Loccoz, P.; Krebs, C.; Huynh, B. H.; Marzilli, L. A.; Cotter, R. J.; Kaderli,
S.; Zuberbuehler, A. D. J. Am. Chem. Soc. 2001, 123, 6183-6184.
(29) Tolman and co-workers report a related methodology, wherein a copper-
(I) complex is added to another side-on dioxygen-Cu complex; this leads
to a bis-µ-oxo dicopper(III) product. See J. Am. Chem. Soc. 2002, 124,
10660.
(30) Compounds 3 and 5 do not epoxidize menadione, the former presumably
due to its thermal instability or its similarity to the behavior of
[(F20TPP)Fe(O2)]- (ref 230).
(31) Kamaraj, K.; Kim, E.; Galliker, B.; Zakharov, L. N.; Rheingold, A. L.;
Zuberbuehler, A. D.; Karlin, K. D. J. Am. Chem. Soc. 2003, 125,
6028-6029.
Acknowledgment. We thank Professor Joan Valentine (UCLA)
for encouraging the approach employed in this report, i.e. reactivity
of species like 3 with copper complexes. We thank the National
JA036632D
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