Dioxygen activation by mononuclear nonheme iron(II) complexes generates iron-oxygen intermediates in the presence of an NADH analogue and proton

Article abstract of DOI:10.1021/ja905691f

(Chemical Equation Presented) One primary goal in biomimetic research is to understand mechanisms of dioxygen activation, structures of reactive intermediates, and reactivities of the intermediates involved in catalytic oxidation reactions by metalloenzym

Full text of DOI:10.1021/ja905691f

Published on Web 09/11/2009
Dioxygen Activation by Mononuclear Nonheme Iron(II) Complexes Generates
Iron-Oxygen Intermediates in the Presence of an NADH Analogue and Proton
†,‡
†
,‡
,§
,†
Seungwoo Hong, Yong-Min Lee, Woonsup Shin,* Shunichi Fukuzumi,* and Wonwoo Nam*
Department of Chemistry and Nano Science, Department of Bioinspired Science, Ewha Womans UniVersity, Seoul
20-750, Korea, Department of Chemistry and Interdisciplinary Program of Integrated Biotechnology, Sogang
1
UniVersity, Seoul 121-742, Korea, and Department of Material and Life Science, Graduate School of Engineering,
Osaka UniVersity, SORST, Osaka 565-0871, Japan
Received July 10, 2009; E-mail: shinws@sogang.ac.kr; fukuzumi@chem.eng.osaka-u.ac.jp; wwnam@ewha.ac.kr
One primary goal in biomimetic research is to understand
mechanisms of dioxygen activation, structures of reactive inter-
mediates, and reactivities of these intermediates in oxidation
reactions by metalloenzymes such as heme and nonheme iron
Scheme 1
1
oxygenases. Extensive mechanistic studies have been carried out
on synthetic iron-oxygen adducts such as iron(III)-hydroperoxo
and iron(IV)-oxo complexes, mostly formed using artificial oxidants
1
8
2 2
such as iodosylarenes, peroxy acids, and H O . However, enzymes
band at 548 nm (Figure 1) with the known ꢀ value of 1. In addition,
instead use dioxygen and electrons plus protons or cofactors (e.g.,
the yield of 1 was found to be maximal when 5 equiv of BNAH
and 1.4 equiv of HClO were added to the reaction solution (SI,
Figure S3). Under these conditions and in an O -saturated solution,
a tetrahydropterin or an R-keto acid) in generating iron-oxygen
4
2
intermediates. Therefore, the use of O
2
as the primary oxidant and
2
oxygen source in studies on synthetic iron complexes is of
fundamental importance. However, there are many intrinsic prob-
lems in this approach, and only a few examples exist.
the rate constant for this reaction, k , was determined to be 8.3 ×
obs
-3
-1 11
III
2+
10 s . Similarly, the formation of [(Bn-TPEN)Fe -OOH]
3
-6
II
2+
(2) was not observed when [Fe (Bn-TPEN)] reacted with O in
2
Nam and co-workers and Banse, Que and co-workers have
independently reported the generation of nonheme iron(IV)-oxo
the presence of BNAH and HClO in CH CN. However, a change
4
3
of solvent from CH CN to CH OH led to the formation of 2 (SI,
3
3
5,6
complexes by activating O
generation of [(TMC)Fe (O)] in the reaction of [Fe (TMC)] and
2
.
The former group demonstrated the
Figure S4 for UV-vis and EPR spectra; also see Figure S5 for
IV
2+
II
2+
II
2+
spectral data of 2 prepared in the reaction of [Fe (Bn-TPEN)]
5,7
9
O
2
3 3
in solvent mixtures of CH CN/alcohols or CH CN/ethers,
and H O in CH OH). In these reactions, both BNAH and HClO
2
2
3
4
whereas the latter group observed the formation of an iron(IV)-oxo
were required to generate the iron(III)-hydroperoxo complexes.
The activation of O by [Fe (TMC)] was also investigated in
2
II
2+
II
2+
complex in the reaction of [Fe (TMC-py)] and O
2
in the presence
-
6,7
II
2+
of an electron (BPh
4
4
) and proton source (HClO ). In those reactions,
4 3
the presence of BNAH and HClO in CH CN. While [Fe (TMC)]
5
IV
2+
12
however, the formation of iron(III)-hydroperoxo species, which are
precursors to the iron(IV)-oxo intermediates, was not observed. In the
present work, we report the generation of nonheme iron(III)-hydro-
3
was air-stable in CH CN, it converted to [(TMC)Fe (O)] (3)
-3
-1
in >90% yield with a kobs value of 6.4 × 10
s
upon addition of
1 equiv each of BNAH and HClO in CH CN at room temperature
In this reaction, the generation of
[(TMC)Fe -OOH] was not detected, probably due to this
4
3
1
1
peroxo and iron(IV)-oxo intermediates by activating O
2
in the presence
(Figure 2).
III
2+
of a biologically important electron donor, a dihydronicotinamide
adenine dinucleotide (NADH) analogue, and an acid; the formation
of iron(III)-hydroperoxo and iron(IV)-oxo complexes was found to
depend on the supporting ligands (Scheme 1, pathway A with N4Py
and Bn-TPEN and pathway B with TMC; see ligand structures in the
intermediate’s instability. Indeed, it was shown previously that the
II
2+
reaction of [Fe (TMC)] and H O afforded 3 rather than
2
2
III
2+
12
[(TMC)Fe -OOH] in CH CN.
3
As shown above, solvent (i.e., alcohol) plays a key role in
generating the iron(III)-hydroperoxo complexes in the reactions of
7
Supporting Information (SI), Figure S1).
Low-spin iron(II) complexes bearing N4Py and Bn-TPEN
II
2+
II
2+
ligands, [Fe (N4Py)] and [Fe (Bn-TPEN)] , are air-stable in
8
,9
CH
(
3
CN.
When we added 1-benzyl-1,4-dihydronicotinamide
BNAH; see structure in SI, Figure S1) and HClO
solution of [Fe (N4Py)] , no reaction took place. Interestingly,
when we dissolved [Fe (N4Py)] in CH
1
0
4
3
to a CH CN
II
2+
II
2+
3
OH and added BNAH
, the color of the
and HClO to the solution in the presence of O
4
2
solution changed from yellow to purple within 3 min at 0 °C. By
recording UV-vis and EPR spectra of the intermediate, we have
III
2+
confirmed the formation of [(N4Py)Fe -OOH] (1) (Figure 1;
also see SI, Figure S2 for spectral data of 1 prepared in the reaction
II
2+
8
2 2 3
of [Fe (N4Py)] and H O in CH OH). The yield of 1 was
determined to be ∼90% by comparing the intensity of the absorption
Figure 1. UV/vis spectral changes showing the formation of 1 (blue line)
II
†
in the reaction of [Fe (N4Py)](ClO
4
)
2
(0.5 mM) and O
2
in the presence of
Ewha Womans University.
Sogang University.
‡
BNAH (0.7 mM) and HClO (2.5 mM) in CH OH at 0 °C. Inset shows
4
3
§
Osaka University.
X-band EPR spectrum of 1 (1.0 mM) at 4 K.
1
3910 9 J. AM. CHEM. SOC. 2009, 131, 13910–13911
10.1021/ja905691f CCC: $40.75  2009 American Chemical Society

C O M M U N I C A T I O N S
In conclusion, we have reported the first example showing the
generation of nonheme iron(III)-hydroperoxo and iron(IV)-oxo
complexes by activating O with a biologically important electron
2
donor, an NADH analogue, and an acid. The formation of the
iron(III)-hydroperoxo and iron(IV)-oxo complexes was found to
depend on the supporting ligands. We have also demonstrated that
III/II
it is high-spin nonheme iron(II) complexes with low Fe
redox
2
potentials which are able to bind and activate O to generate
iron-oxygen intermediates.
Acknowledgment. The research was supported by KOSEF/MEST
through the CRI Program (to W.N.) and WCU Program (R31-2008-
00-10010-0) (to S.F. and W.N.), KOSEF (R01-2008-000-20704-0)
(to W.S.), and a Global COE program from the Ministry of Education,
Culture, Sports, Science and Technology, Japan (to S.F.).
Figure 2. (a) UV/vis spectral changes showing the formation of 3 (red
II
line) in the reaction of [Fe (TMC)](CF
presence of BNAH (0.5 mM) and HClO
3
SO
(0.5 mM) in CH
b) ESI MS spectrum of 3. Peaks at m/z of 184.5 and 477.0 correspond to
3
)
2
(0.5 mM) and O
2
in the
0
4
3
CN at 25 °C.
(
[
IV
2+
IV
+
3 3 3
Fe (TMC)(O)(CH CN)] and [Fe (TMC)(O)(CF SO )] , respectively.
Insets show the observed (left panel) and calculated (right panel) isotope
distribution patterns.
Supporting Information Available: Experimental details and
spectroscopic and cyclic voltammetric data. This material is available
free of charge via the Internet at http://pubs.acs.org.
Scheme 2
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(7) Abbreviations: TMC ) 1,4,8,11-tetramethyl-1,4,8,11-tetraaza-cyclotetrade-
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II
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+
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3
CN
0′
II
2+
0′
II
2+
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II
2+
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III/II
a low Fe
2
redox potential are able to bind and activate O to
1
936.
form iron-oxygen adducts in the presence of an NADH analogue
and an acid. It is worth noting that it is high-spin Fe(II) species
(
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2
which bind and activate O in heme and nonheme iron enzymes
2
,13
and in bleomycin.
A proposed mechanism for O
here is depicted in Scheme 2. The reaction is initiated by O
(
(
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1
2
-activation in the complexes described
-binding
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Y.-M.; Nam, W. J. Am. Chem. Soc. 2008, 130, 15134–15142. Also, see
SI, Figure S3b.
2
by a high-spin iron(II) complex that leads to the generation of an
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IV
2+
(
14) We have previously proposed that the formation of [(TMC)Fe (O)] (3)
II
2+
from the reaction of [Fe (TMC)] and O
alcohols or CH CN/ethers occurs via O-O bond cleavage of a (µ-1,2-
peroxo)diiron(III) intermediate: see ref 5.
2 3
in solvent mixtures of CH CN/
3
III
2+
14
[
(TMC)Fe -OOH] intermediate (pathway C).
JA905691F
J. AM. CHEM. SOC. 9 VOL. 131, NO. 39, 2009 13911