Nonheme FeIVO Complexes That Can Oxidize the C-H Bonds of Cyclohexane at Room Temperature

Article abstract of DOI:10.1021/ja037288n

Nonheme oxoiron(IV) complexes of two pentadentate ligands, N4Py (N,N-bis(2-pyridylmethyl)-bis(2-pyridyl)methylamine) and Bn-tpen (N-benzyl-N,N′,N′-tris(2-pyridylmethyl)-1,2-diaminoethane), have been generated and found to have spectroscopic properties similar to the closely related tetradentate TPA (tris(2-pyridylmethyl)amine) complex reported earlier. However, unlike the TPA complex, the pentadentate complexes have a considerable lifetime at room temperature. This greater thermal stability has allowed the hydroxylation of alkanes with C-H bonds as strong as 99.3 kcal/mol to be observed at room temperature. Furthermore, a large deuterium KIE value is found in the oxidation of ethylbenzene. These observations lend strong credence to postulated mechanisms of mononuclear nonheme iron enzymes that invoke the intermediacy of oxoiron(IV) species. Copyright

Full text of DOI:10.1021/ja037288n

Published on Web 12/23/2003
Nonheme FeIVO Complexes That Can Oxidize the C-H Bonds of Cyclohexane
at Room Temperature
Jo´zsef Kaizer,† Eric J. Klinker,† Na Young Oh,‡ Jan-Uwe Rohde,† Woon Ju Song,‡ Audria Stubna,§
Jinheung Kim,| Eckard Mu¨nck,*,§ Wonwoo Nam,*,‡ and Lawrence Que, Jr.*,†
Department of Chemistry and Center for Metals in Biocatalysis, UniVersity of Minnesota,
Minneapolis, Minnesota 55455, Department of Chemistry and DiVision of Nano Sciences, Ewha Womans UniVersity,
Seoul 120-750, Korea, Department of Chemistry, Carnegie Mellon UniVersity, Pittsburgh, PennsylVania 15213,
and Department of Chemical Technology, Changwon National UniVersity, Changwon 641-773, Korea
Received July 15, 2003; E-mail: que@chem.umn.edu
Postulated mechanisms for the functionalization of aliphatic C-H
bonds by mononuclear nonheme iron(II) enzymes often invoke
C-H bond cleavage by an FeIVdO intermediate that is generated
by dioxygen activation.1,2 Such transformations include the hy-
droxylation of prolyl or aspargine residues by enzymes that are
involved in sensing hypoxia in mammalian cells,3 ring-forming
reactions in the biosynthesis of â-lactam antibiotics such as
penicillin, cephalosporin, and clavulanic acid,4 and the first step in
the biodegradation of the herbicide 2,4-D.5 The general features of
these transformations parallel the mechanism widely accepted for
heme enzymes such as cytochrome P450, except that the nonheme
enzymes employ an FeII/FeIVdO redox couple in place of the
formally FeIII/FeVdO couple associated with heme enzymes. In
support, direct spectroscopic evidence for an iron(IV) intermediate
in this class of enzymes has just been reported for the 2-oxoglut-
arate-dependent enzyme TauD.6 While it is well established that
Figure 1. Electronic spectra of 1 and 2 in CH3CN at 25 °C. Inset:
the high-valent heme intermediate, best described as [FeIV(O)-
Correlation between the number of pyridine ligands and the absorption
maxima of [FeIV(O)(L)] complexes (L ) N4Py (a), Bn-tpen (b), TPA (c),
(porphyrin π-cation radical)]+, can hydroxylate the C-H bonds of
cyclohexane (DC-H ≈ 99.3 kcal/mol),7 the proposed mechanisms
for nonheme enzymes raise the interesting question as to whether
the corresponding one-electron reduced FeIVdO unit in a nonheme
ligand environment has sufficient oxidizing power to cleave
aliphatic C-H bonds as strong as those found on the C-3 and C-4
positions of proline. We recently reported the high-yield generation
of synthetic oxoiron(IV) complexes using tetradentate N4 ligands
such as the macrocyclic TMC and the tripodal TPA ligands8,9 and
obtained a high-resolution X-ray structure of the former.9a While
the TMC complex can effect oxygen-atom transfer only to PPh3 at
-40 °C, the TPA complex is able to epoxidize cyclooctene at this
temperature. We now report the synthesis and characterization of
corresponding FeIVdO complexes of the pentadentate N5 ligands
N4Py and Bn-tpen.8 Most striking of their properties are their higher
temperature stability and their ability to hydroxylate C-H bonds
as strong as those in cyclohexane.
Treatment of [FeII(N4Py)(CH3CN)]2+ 10 with excess solid PhIO
in CH3CN at 25 °C affords a green species 1 that persists for several
days (t1/2 ≈ 60 h). The green color is associated with a band at 695
nm (ꢀ 400 M-1 cm-1) (Figure 1) with a shoulder near 800 nm.
Like treatment of [FeII(Bn-tpen)(O3SCF3)]+ 11 also affords a green
species 2 with λmax at 739 nm (ꢀ 400 M-1 cm-1) and a shoulder
near 900 nm, but this species is less stable (t1/2 ≈ 6 h). Similar
near-IR bands have been reported for [FeIV(O)(TMC)(CH3CN)]2+
(3) (λmax 820 nm) and [FeIV(O)(TPA)(CH3CN)]2+ (4) (λmax 720
nm).9
BPMCN (d), and TMC (e)).
The nature of these green species can be established by other
spectroscopic techniques. Thus, high-resolution electrospray mass
spectrometry reveals respective molecular ions at m/z 538.0559
and 644.1227, mass values fully consistent with their formulation
as {[FeIV(O)(N4Py)](ClO4)}+ (1) (m/z calcd 538.0583) and
{[FeIV(O)(Bn-tpen)](O3SCF3)}+ (2) (m/z calcd 644.1247) ions
(Figure S1, Supporting Information). Mo¨ssbauer spectra confirm
the presence of the iron(IV) state in both complexes, as indicated
by ∆EQ and δ values of 0.93 mm/s and -0.04 mm/s for 1 and
0.87 and 0.01 mm/s for 2 (Figure S2, Supporting Information). The
isomer shifts are similar or identical to the 0.01 mm/s value
associated with 4. Thus, 1 and 2 belong to an emerging class of
low-spin FeIVdO complexes with nonheme ligand environments
with a near-IR spectral signature. As illustrated in the inset of Figure
1, the λmax values of the five established oxoiron(IV) complexes
correlate well with the number of pyridine ligands. The observation
that more pyridine ligands give rise to higher energy transitions
supports the notion that this near-IR band is ligand field in character,
rather than charge transfer in origin,9 but more detailed investiga-
tions (in progress) are needed to establish the spectral assignment.
Although closely related to 4, 1 and 2 are thermally more stable,
presumably due to the pentadentate ligands in the latter two
complexes. Despite their higher room-temperature stability, 1 and
2 react with a number of hydrocarbons at room temperature. Figure
2 shows that the addition of 25 equiv of triphenylmethane results
in a rapid decay of 1 concomitant with the nearly quantitative
appearance of its iron(II) precursor (λmax 450 nm) with an isosbestic
point at 560 nm. Ph3C-OH is obtained in 90% yield, demonstrating
† University of Minnesota.
‡ Ewha Womans University.
§ Carnegie Mellon University.
| Changwon National University.
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J. AM. CHEM. SOC. 2004, 126, 472-473
10.1021/ja037288n CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
for a synthetic nonheme iron complex. Such large isotope effects
have been observed for hydrogen atom abstraction reactions by the
iron(IV) intermediates of the monoiron TauD6b and the diiron
enzyme methane monooxygenase,15 for which hydrogen tunneling
mechanisms may be involved. The observation of a large kinetic
isotope effect for a synthetic mononuclear FeIV(O) species provides
the opportunity to explore this phenomenon with a simple system.
In summary, we have obtained and characterized nonheme
oxoiron(IV) complexes of two pentadentate ligands with properties
similar to the closely related tetradentate TPA counterpart reported
earlier. However, unlike the TPA complex, the pentadentate
complexes have considerably longer lifetimes at room temperature.
This greater thermal stability has allowed the hydroxylation of
alkanes with C-H bonds as strong as 99.3 kcal/mol to be observed
with large deuterium KIEs. These observations lend strong credence
to postulated mechanisms of mononuclear nonheme iron enzymes
that invoke the intermediacy of oxoiron(IV) species.
Figure 2. Conversion of 1 (1 mM) to its iron(II) precursor in CH3CN
upon addition of Ph3CH at 25 °C. Inset: time course of the decay of 1 (2
mM) monitored at 695 nm upon addition of 0.1 M Ph3CH (A), 0.5 M PhEt
(B), and 0.5 M PhEt-d10 (C) in CH3CN at 25 °C.
Acknowledgment. This work was supported by the National
Institutes of Health (GM-33162 to L.Q. and GM-22701 to E.M.),
the Ministry of Science and Technology of Korea through the
Creative Research Initiative Program (W.N.), and an NSF graduate
fellowship to A.S.
Supporting Information Available: Detailed procedures, figures
of electrospray mass spectra and Mo¨ssbauer spectra of 1 and 2, and
table listing results of hydrocarbon oxidation experiments associated
with Figure 3 (PDF). This material is available free of charge via the
Internet at http://pubs.acs.org.
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Figure 3. Correlation between the C-H bond dissociation energies of
various hydrocarbons and log k2′ (25 °C) for their reactions with 1 (b) or
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correlation between log k2′ and C-H bond dissociation energy
(DC-H) from Ph3C-H to cyclohexane. A similar plot is observed
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capable of oxidizing hydrocarbons with stronger C-H bonds.
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of the substrate with the stronger C-H bond. More significantly,
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