Structures of nonheme oxoiron(IV) complexes from X-ray crystallography, NMR spectroscopy, and DFT calculations

Article abstract of DOI:10.1002/anie.200500485

(Figure Presented) Stabilizing the oxoiron(IV) unit: From a combination of X-ray crystallography, NMR spectroscopy, and DFT calculations, the relative thermal stabilities of two oxoiron(IV) complexes with pentaaza ligands, such as that shown in the picture, can be ascribed to the number of pyridine rings that are oriented parallel to the Fe= O bond. (Fe pink, N blue, O red, C black.).

Full text of DOI:10.1002/anie.200500485

Angewandte
Chemie
Communications
The structures of recently discovered non-heme oxoiron(iv) complexes
of two pentadentate ligands have been deduced, one by X-ray
crystallography and the other by 1H NMR spectroscopy. Detailed
experimental and theoretical studies are described by L. Que, Jr.,
C. J. Cramer et al. on the following pages.
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DOI: 10.1002/anie.200500485
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Oxoiron(iv) Complexes
spectroscopy, and DFT (density functional theory) calcula-
tions, and their relative thermal stabilities.
Structures of Nonheme Oxoiron(iv) Complexes
from X-ray Crystallography, NMR Spectroscopy,
and DFT Calculations**
Complexes 1 and 2 exhibit half-lives of approximately 60
and 6 h, respectively, at room temperature. The greater
thermal stability of 1 allowed the isolation of single crystals
for X-ray crystal structural analysis (Figure 1) to provide only
Eric J. Klinker, Jꢀzsef Kaizer, William W. Brennessel,
Nathaniel L. Woodrum, Christopher J. Cramer,* and
Lawrence Que, Jr.*
Oxoiron(iv) species are frequently invoked as reactive
intermediates in the oxygen-activation mechanisms of mono-
nuclear nonheme iron enzymes.[1] In 2003, the trapping of the
first nonheme oxoiron(iv) intermediate in the reaction of O2
with the 2-oxoglutarate-dependent enzyme TauD, which was
complexed with 2-oxoglutarate and its substrate taurine, was
reported.[2–5] Contemporaneously, the first examples of well-
characterized synthetic oxoiron(iv) complexes with nonheme
ligand environments were also described.[6,7] The presumably
reactive oxoiron(iv) units could be stabilized sufficiently by
tetraaza ligands such as macrocyclic tetramethylcyclam
(TMC) and tripodal tris(2-pyridylmethyl)amine (TPA) to
allow their spectroscopic characterization at low temperature.
In the case of the TMC complex, its considerable stability
allowed it to be crystallized and its structure to be determined
by X-ray crystallography. These results represented the first
high-resolution structural data for any oxoiron(iv) complex,
heme or nonheme. Subsequently it was found that the
oxoiron(iv) unit could also be generated from precursor
iron(ii) complexes of pentadentate pentaaza ligands such as
N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine
Figure 1. Molecular structure of 1 (a) and top views of space-filling
models of 1 (b) and 3 (c). Metal–ligand bond lengths [ꢀ] for 1:
Fe–O 1.639(5), Fe–N1 2.033(8), Fe–N2 1.964(5), Fe–N3 1.949(5).
the second high-resolution structure of an oxoiron(iv) com-
ꢀ
plex. The X-ray crystal structure of 1 shows an Fe O bond
(N4Py) and N-benzyl-N,N’,N’-tris(2-pyridylmethyl)-1,2-di-
aminoethane (Bn-TPEN) by treatment with a peracid or
PhIO. In fact, [FeIV(O)(N4Py)]2+ (1) and [FeIV(O)(Bn-
TPEN)]2+ (2) could be produced in high yields at room
temperature by reaction with excess solid iodosylbenzene in
CH3CN to afford solutions with significant thermal stability.[8]
Herein, we report insight into the structures of 1 and 2
obtained from a combination of X-ray crystallography, NMR
length of 1.639(5) ꢀ, a value that is essentially identical to the
length of 1.646(3) ꢀ reported for the analogous bond in
[Fe(O)(TMC)(NCCH3)](SO3CF3)2 (3).[6] Trans to the oxo
ligand in 1 is the amine nitrogen atom that holds the
ꢀ
pentadentate ligand together, with an Fe N1 bond length of
2.033(8) ꢀ, the longest metal–ligand bond in the molecule.
The O1, Fe, and N1 atoms are nearly colinear with an O1-Fe-
N1 angle of 178.6(3)8. Coordinated in the equatorial plane are
the four pyridine nitrogen atoms, whose rings are aligned
parallel to the Fe–O axis, and the iron atom lies 0.252 ꢀ above
the plane subtended by these four pyridyl nitrogen atoms
[*] N. L. Woodrum, Prof. Dr. C. J. Cramer
Department of Chemistry and
Supercomputer Institute
ꢀ
towards the oxo ligand. Interestingly, the equatorial Fe N
bond lengths are on average 1.957(5) ꢀ; these bonds are
shorter than the corresponding equatorial bonds in 3 by 0.1 ꢀ
and reflect the stronger bonding ability of a pyridine moiety
relative to a tertiary amine.
University of Minnesota
207 Pleasant Street SE, Minneapolis, MN 55455 (USA)
Fax: (+1)612-624-2006
E-mail: cramer@chem.umn.edu
Figures 1b and c compare the top views of space-filling
models of 1 and 3 and reveal a large difference in the
accessibility of the oxoiron unit in the two complexes.
Whereas the hydrogen atoms of the TMC macrocycle nestle
nicely around the oxo atom in 3 and restrict access,[6] the oxo
group in 1 is much more exposed not only from the top of the
molecule but also along channels that form between adjacent
pyridine rings. This difference may rationalize the relative
reactivities of the two complexes. While 3 is quite inert toward
E. J. Klinker, Dr. J. Kaizer, W. W. Brennessel, Prof. Dr. L. Que, Jr.
Department of Chemistry and
Center for Metals in Biocatalysis
University of Minnesota
207 Pleasant Street SE, Minneapolis, MN 55455 (USA)
Fax: (+1)612-624-7029
E-mail: que@chem.umn.edu
[**] This work was supported by grants from the National Institutes of
Health (GM-33162 to L.Q.) and the National Science Foundation
(CHE-0203346 to C.J.C.).
ꢀ
hydrocarbon substrates, at room temperature 1 can attack C
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
H bonds as strong as those in cyclohexane.[6,8]
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Communications
Single crystals of 2 have not yet been isolated, so its
structure must be deduced by alternative means. A recent
EXAFS (extended X-ray absorption fine spectrum) study[9]
ꢀ
ꢀ
revealed the presence of a short Fe O bond of 1.67 ꢀ and Fe
N bond lengths that average 2.00 ꢀ, as expected, but no
insight was gained into how the pentadentate ligand wraps
around the metal center. The flexibility of the ligand requires
three conformational isomers, if we neglect enantiomers, to
be considered (Figure 2). Isomer A contains two pyridine
rings that eclipse the Fe–O axis and a third that is perpen-
dicular to it, as found in the structure of the iron(ii)
precursor.[9] In isomer B one ring eclipses the Fe–O axis and
two are perpendicular to it, whereas in isomer C two rings are
perpendicular to the Fe–O axis and the other is coordinated
trans to the oxygen atom.
We found 1H NMR spectroscopy to be a very useful
technique to probe the structures of the nonheme oxoiron(iv)
complexes, and the spectra of 1 and 2 are shown in Figure 3.
The S = 1 iron(iv) centers of 1 and 2 have favorable electronic
relaxation properties that give rise to relatively sharp and
well-resolved, paramagnetically shifted proton resonances
that span 200 ppm. The number of signals observed for 1 is
consistent with the presence of mirror symmetry, as estab-
lished from the solid-state structure. Two sets of pyridine
resonances (b, b’, and g) can be readily identified by a COSY
experiment (see Supporting Information). The shift pattern
for the protons of the pyridine rings is unique for the low-spin
iron(iv) center, with one b proton shifted downfield and the b’
proton shifted upfield. In iron(ii) and iron(iii) pyridine
complexes, both b protons are typically shifted downfield
with comparable paramagnetic shifts.[10,11]
Figure 3. 1H NMR spectra of 1 (a) and 2 (b, and insets) in CD3CN.
Peaks from pyridine ring protons are assigned based on cross peaks
identified in COSY spectra. The left inset shows the expanded region
near d=0 ppm (0.5ꢁ) for 2 and reveals the third set of pyridine ring
protons, while the right inset shows the ꢀ30>d>ꢀ75 ppm region
(10ꢁ) of 2.
of the corresponding 5-Me-Bn-TPEN complex 4 shows
the disappearance of the b’c proton, thereby leading us
to assign the c set of pyridine protons to the unique
pyridine on the Bn-TPEN ligand.
The presence of a pyridine ring with a unique shift
pattern in 2 suggests that the Bn-TPEN ligand adopts a
wrapping mode that corresponds to isomer
A
(Figure 2). The two pyridines that display similar
shift patterns to those found in 1 would correspond
to the two that are parallel to the Fe–O axis, while the
pyridine that lies perpendicular to the Fe–O axis would
give rise to the unusual shift pattern. The difference in
their paramagnetic shifts can be easily rationalized by
the fact that these pyridines must interact differently
with iron d orbitals that have differing amounts of unpaired
spin density.
To provide a theoretical foundation upon which to
interpret our observations, DFT calculations were carried
out to assess the relative energies of the three possible
isomers of 2 (Figure 2). Of several models examined, the pure
density functional BPW91 model provided an optimized
structure for 1 that agreed well with crystallographic data
(0.0957 ꢀ root-mean-square deviation over all heavy atoms;
see Supporting Information for results using all functionals).
Primarily on this basis, BPW91 was chosen for the study of 2.
Figure 2. The three possible isomers (A–C) of [FeIV(O)(R-TPEN)]2+ complexes. R=Bn or
Me.
Not surprisingly, the 1H NMR spectrum of 2 is more
complex as a result of the lower symmetry of this complex.
Two sets of pyridine b, g, and b’ protons are readily identified
from their COSY cross peaks (see Supporting Information)
and found at chemical shifts that are comparable to those
found for 1. Their integrations indicate that these peaks
account for only two of the three pyridine rings in the
complex. Examination of a second COSY spectrum with a
narrower spectral width (see Supporting Information) reveals
the b, g, and b’ protons of the third pyridine. These protons
exhibit smaller paramagnetic shifts and have a distinct shift
pattern in which both b and b’ peaks are shifted upfield and
the peak for the g proton is shifted downfield. The spectrum
ꢀ
Table 1 provides Fe O bond lengths and relative energies for
all optimized structures and spin states. The triplet state is
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Table 1: Relative BPW91 energies (E [kcalmolꢀ1]) for 2A–C and Fe–ligand bond lengths (ꢀ; for S=1
metrical parameters for this com-
isomers only).[a]
plex and shows the expected ligand
topology in which all four pyridines
are oriented approximately paral-
1[b]
2A
0.0
2B
5.3
2C
E (S=1)[c]
E (S=2)[c]
Fe-O
12.5
=
lel to the Fe O axis. In the absence
16.6
1.640
19.0
1.643
of a crystal structure for 2, NMR
spectral data and DFT calculations
clearly favor 2A as the most stable
isomer. We thus conclude that
pyridine rings aligned parallel to
1.639
1.645
Fe-N1
Fe-N2
Fe-N3
Fe-N4
Fe-N5
Fe-Nav
2.082 (amine, ax)
1.976 (py k)
1.983 (py k)
2.078 (amine)
2.022 (py ?)
1.976 (py k)
1.990 (py k)
2.132 (amine, ax)
2.040
2.010 (amine)
2.040 (py ?)
1.976 (py k)
2.002 (py ?)
2.191 (amine, ax)
2.044
2.051 (amine)
2.058 (py ?)
2.042 (py ?)
2.104 (py, ax)
2.004 (amine)
2.052
=
the Fe O bond contribute signifi-
2.000
cantly to the stability of the oxoir-
on(iv) unit and allow such com-
plexes to be observed at room
temperature.
[a] See Supporting Information for Cartesian coordinates of the geometry-optimized structures of the
three isomers 2A–C. [b] Crystallographic bond lengths for 1 included for comparison. [c] Energy for the
S=1 state of isomer 2A set to zero. py=pyridine, ax=axial.
favored over the pentet state in each of the two lower-energy
isomers (the pentet was not converged for isomer C), and all
further discussion refers only to triplet states.
Experimental Section
Complexes 1 and 2 were generated from their respective iron(ii)
precursors following reported procedures,[8] while the generation of 4
followed a similar protocol. The synthesis for the precursor to 4,
[(5-Me-Bn-TPEN)FeII(OSO2CF3)](SO3CF3), is described in the Sup-
porting Information.
Of the three isomers of 2, A is predicted to be lowest in
energy, with isomers B and C lying 5.3 and 12.5 kcalmolꢀ1
higher in energy, respectively.[12] When the iron atom is
removed and the relative energies of the frozen ligands are
computed at the same level of theory, the relative energies of
A, B, and C are found to be 1.0, 0.0, and 2.4 kcalmolꢀ1,
respectively. Thus, the relative energies of the iron complexes
do not derive from differences in steric energy in the
supporting ligand but rather from interactions of the ligand
1H NMR spectra were recorded on a Varian Inova VI-500
spectrometer at ambient temperature, with reported 1H NMR
chemical shifts (d [ppm]) referenced to residual solvent peaks. The
COSY spectrum for 1 was collected using 256 points in t1 with a
spectral width of 54.3 kHz and a delay of 30 ms. The COSY spectra
for 2 were collected using 256 points in t1 with spectral widths of 47.8
and 19.7 kHz and a delay of 30 ms.
=
with the Fe O moiety.
Examination of the data in Table 1 suggests that the
metal–ligand bond lengths rationalize the relative stabilities
of the three isomers of 2. Equatorial pyridine ligands aligned
X-ray crystal structure data for 1: Blue needles were isolated
upon layering pentane on
a solution of 1 in acetonitrile:
C27H27Cl2FeN7O9, monoclinic, space group Cm, a = 11.955(4), b =
17.954(5), c = 7.084(2) ꢀ, b = 93.708(5)8, V= 1517.3(8) ꢀ3, Z = 2,
=
ꢀ
parallel to the Fe O axis always have shorter Fe N bonds
1calcd = 1.577 gcmꢀ3
,
crystal dimensions: 0.32 ꢁ 0.12 ꢁ 0.04 mm3;
=
than those aligned perpendicular to the Fe O axis. This
Bruker CCD diffractometer; MoKa radiation, 173(2) K; 2qmax
=
shorter distance contributes to the ability of parallel pyridines
to stabilize the high-valent iron center through electron
donation better than perpendicular pyridines, as judged by
second-order perturbation theory in the natural bond orbital
50.18, 5606 reflections, 2669 independent (Rint = 0.0454), direct
methods; multiscan absorption correction (m = 0.739 mmꢀ1); refine-
ment (on F2) with SHELXTL-Plus (version 5.10), 301 parameters, 126
restraints, R1 = 0.0499 (I > 2s) and wR2 (all data) = 0.1178, GOF =
1.046, max/min residual electron density: 0.435/ꢀ0.211 eꢀꢀ3. CCDC
261401 (1) contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from the Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/
cif. See Supporting Information for additional experimental
details.
Computational Methods: The molecular geometry of [Fe(O)-
(N4Py)]2+ (S = 1) was optimized at the unrestricted BLYP,[15,16]
BPW91,[16,17] BP86,[15, 18,19] BP86-VWN5,[15,19,20] B3LYP,[15,16, 19]
B3PW91,[15, 17] B3P86,[15,19,20] and BHANDH[15] levels using the
LACVP*[21–23] effective core potential on iron and the 6-31G**[24–29]
basis set on all other atoms. The BPW91 model was found to provide
good agreement with the known crystal structure and was chosen on
this basis for modeling Fe(Me-TPEN) (in Me-TPEN, the benzyl
group of Bn-TPEN is replaced by a methyl group). Three conformers
of Fe(Me-TPEN) were optimized at this level for the S = 1 spin state,
and in the two lowest energy cases for the S = 2 spin state. All
structures were verified as minima by computation of analytical
vibrational frequencies. Calculations were performed using Jaguar
5.0[30] and Jaguar NBO Version 5.0.[31]
[13,14]
ꢀ
(NBO) basis.
The difference in Fe N bond lengths is
easily explained by the greater steric demand of the a hy-
drogen atoms of the pyridines that lie perpendicular to the
=
Fe O axis. Thus, among the three isomers of 2, the most
stable isomer A has one pyridine ring perpendicular and two
=
rings parallel to the Fe O axis to give rise to an average bond
ꢀ
length of 2.040 ꢀ over all Fe N bonds. The less-stable
isomers, by contrast, both contain two perpendicular equato-
rial pyridines, with the remaining ring either parallel (B) or
trans to the oxo atom (C). These differences give rise to
ꢀ
average Fe N bond lengths of 2.044 and 2.052 ꢀ, respectively.
For comparison, all four of the pyridine rings in the N4Py
=
complex 1 are oriented parallel to the Fe O axis with an
ꢀ
average Fe N bond length of 2.00 ꢀ and thereby it achieves
maximum stabilization among the four structures. Not
surprisingly, the half-life of 1 is an order of magnitude greater
than that of 2.
In summary, we have gained structural insight into novel
oxoiron(iv) complexes with pentadentate pentaaza ligands by
a combination of X-ray crystallography, NMR spectroscopy,
and DFT calculations. The X-ray structure of 1 establishes the
Received: February 8, 2005
Revised: March 3, 2005
Published online: May 25, 2005
Angew. Chem. Int. Ed. 2005, 44, 3690 –3694
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3693

Communications
Keywords: bioinorganic chemistry · density functional
.
calculations · iron · nitrogen heterocycles · NMR spectroscopy
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