Mononuclear nonheme ferric-peroxo complex in aldehyde deformylation

Article abstract of DOI:10.1039/b505562h

A mononuclear nonheme ferric-peroxo complex bearing a macrocyclic tetradentate N4 ligand, [(TMC)Fe^III-O₂]₊, was prepared and used in mechanistic studies of aldehyde deformylation; a catalytic aldehyde deformylation by a nonheme iron(II) complex, [Fe_II(TMC)] ²⁺, and molecular oxygen is reported as well. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b505562h

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Mononuclear nonheme ferric-peroxo complex in aldehyde
deformylation{
Jamespandi Annaraj, Yumi Suh, Mi Sook Seo, Sun Ok Kim and Wonwoo Nam*
Received (in Cambridge, UK) 21st April 2005, Accepted 21st July 2005
First published as an Advance Article on the web 10th August 2005
DOI: 10.1039/b505562h
A mononuclear nonheme ferric-peroxo complex bearing a
+
Addition of 10 equiv. H
(CF SO and 5 equiv. of triethylamine in CF
afforded a blue intermediate 1 with a maximum absorption
2
O
2
to a solution containing Fe(TMC)-
III
macrocyclic tetradentate N4 ligand, [(TMC)Fe –O
2
] , was
3
3
)
2
3
CH OH{ at 0 uC
2
prepared and used in mechanistic studies of aldehyde deformy-
lation; a catalytic aldehyde deformylation by a nonheme
21
21
wavelength lmax at 750 nm (e 600 M cm ) (Fig. 1a). The
electrospray ionization mass spectrum (ESI MS) of 1 exhibits a
prominent ion peak at a mass-to-charge ratio (m/z) of 344.1
II
2+
iron(II) complex, [Fe (TMC)] , and molecular oxygen is
reported as well.
(
Fig. 1b), whose mass and isotope distribution pattern correspond
+
Ferric-peroxo complexes are frequently implicated as key inter-
mediates in oxidation reactions catalyzed by heme and nonheme
to [Fe(III)(TMC)(O
)] (calculated m/z of 344.1) (Fig. 1b, inset).
2
1
2
8
When the reaction was carried out with isotopically labeled H
O
2
1
,2
18
18
2
+
iron enzymes. In heme iron enzymes, the participation of a
ferric-peroxo species as an active oxidant has been invoked in
many cytochrome P450-catalyzed reactions including the aroma-
tization of androgen to estrogen by cytochrome P450 aromatase
and the cleavage of the C-17 side chain of progesterone to form
(90% O-enriched, 2% H
O
2
in water), a mass peak correspond-
)] appeared at m/z of 348.1 (calculated
2
18
ing to [Fe(III)(TMC)( O
1,3,4
androstenedione by progesterone 17a-hydroxylase-17,20-lyase.
Evidence for the ferric-peroxo species behaving as a nucleophile
and attacking an aldehyde carbon has been obtained from
3,4
mechanistic studies of the enzymes and synthetic ferric-peroxo
5–7
porphyrin complexes.
In nonheme iron enzymes, a ferric-peroxo species has also been
proposed as an active oxidant responsible for the cis-dihydroxyla-
2b,8
tion of aromatic compounds catalyzed by Rieske dioxygenases.
Very recently, the crystal structure of a ferric-peroxo intermediate
has been obtained in naphthalene dioxygenase, in which the peroxo
9
ligand is bound to the mononuclear iron in a side-on fashion. In
biomimetic studies, it has been well-documented that ferric-peroxo
complexes are easily prepared by the deprotonation of their corres-
10
ponding ferric-hydroperoxides upon addition of base (eqn. 1).
Although nonheme ferric-peroxo complexes bearing pentadentate
N5 ligands have been well characterized with various spectroscopic
techniques including UV-vis, EPR, mass, M o¨ ssbauer, resonance
1
0
Raman, and X-ray absorption spectroscopy, the reactivity of
nonheme ferric-peroxo complexes has been rarely investigated in
oxidation reactions. In this communication, we report the genera-
tion and characterization of a mononuclear nonheme ferric-peroxo
complex bearing a macrocyclic tetradentate N4 ligand, [(TMC)-
III
+
2
Fe –O ] (1) (TMC 5 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclo-
tetradecane), and its reactivity in aldehyde deformylation. A
catalytic aldehyde deformylation by a nonheme iron(II) complex,
2+
II
Fe (TMC)] , and molecular oxygen (O ) is reported as well.
[
2
(
1)
Fig. 1 (a) UV-vis spectral changes showing the formation of 1 upon
II
2+
addition of H
and triethylamine (10 mM) in CF
ionization mass spectrum of 1. Insets show observed isotope distribution
2
O
2
(20 mM) to a solution containing [Fe (TMC)] (2 mM)
Department of Chemistry, Division of Nano Sciences, and Center for
Biomimetic Systems, Ewha Womans University, Seoul, 120-750, Korea.
E-mail: wwnam@ewha.ac.kr; Fax: +82-2-3277-4441;
Tel: +82-2-3277-2392
3
CH OH at 0 uC. (b) Electrospray
2
16
+
18
+
patterns for [Fe(III)(TMC)( O
2 2
)] (left panel) and [Fe(III)(TMC)( O )]
(
right panel). (c) EPR spectrum of 1. Instrumental parameters: tem-
{
Electronic supplementary information (ESI) available: experimental
details and Figure S1. See http://dx.doi.org/10.1039/b505562h
perature, 4 K; microwaves, 9.05 GHz at 1 mW; modulation, 100 KHz.
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Chem. Commun., 2005, 4529–4531 | 4529

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m/z of 348.1) (Fig. 1b, inset). The X-band EPR spectrum of 1
exhibits an intense signal centered at g 5 4.3 with two absorption-
the formation of ketone as a major product via C–C bond cleavage
is similar to the reaction of cytochrome P450 progesterone
17a-hydroxylase-17,20-lyase (CYP 45017a), in which a ferric-
peroxo porphyrin intermediate is proposed to attack the carbonyl
group of progesterone which leads to the formation of androste-
type features at g # 8.8 and 5.9 (Fig. 1c), typical of a high-spin
III
S 5 5/2) Fe species. On comparison of the spectral features of 1
(
to those of the well-characterized nonheme ferric-peroxo com-
1
0
4
plexes, we conclude that a mononuclear ferric-peroxo complex,
+
nedione and acetate (eqn. 3). The pseudo-first-order rate
III
(TMC)Fe –O
II
] , was generated in the reaction of [Fe (TMC)]
2+
[
2
constants increased proportionally with the 2-PPA concentration,
and H O in the presence of base.
2
leading us to determine a second-order rate constant to be 4.1(2) 6
2
22
21 21
We then investigated the reactivity of 1 in aldehyde deformyla-
tion, with a precedent that the porphyrin analogue of 1 reacts with
10
M
s
(Fig. 2b). By determining the first-order-rate
constants for the deformylation of 2-PPA by 1 from 273 K to
{
1a,7
aldehydes to give the corresponding deformylated products.
Upon addition of 60 equiv. 2-phenylpropionaldehyde (2-PPA)§ to
the solution of 1 (2 mM) at 15 uC in CF CH OH, the intermediate
293 K, we were able to calculate activation parameters of DH 5
2
1
{
21 21
13(1) kcal mol and DS 5 224(2) cal mol
K
(Fig. 2c). It is
] (N4Py 5 N,N-bis(2-pyridyl-
2
III
+
worth noting that [(N4Py)Fe –O
methyl)-N-bis(2-pyridyl)methylamine)
3
2
10g
reverted back to the starting iron complex, showing an isosbestic
also reacts with 2-PPA
point at 450 nm (Fig. 2a). Pseudo-first-order fitting of the kinetic
23 21
much faster than 1 at 230 uC, yielding acetophenone as a major
product.** Further, the nonheme ferric-peroxo complexes (i.e., 1
III
and [(N4Py)Fe –O ] ) react with other electrophiles (e.g., benzoyl
2
data allowed us to determine the kobs value to be 4.6(3) 6 10
s
+
(Fig. 2a, inset), and product analysis of the reaction mixture with
HPLC, LC-MS, GC, and GC-MS revealed that acetophenone was
produced predominantly with the formation of formate (eqn. 2)
chloride and acetic anhydride) at a fast rate. It has been shown in
iron porphyrin studies that the reactions of ferric-peroxo
porphyrins with electrophiles generate high-valent iron(IV)-oxo
(ESI{, Experimental Conditions)."I It is of interest to note that
5
porphyrin intermediates. Thus detailed investigations of the
reactions of nonheme ferric-peroxo complexes with various
11
electrophiles are underway in this laboratory.
ð2Þ
ð3Þ
We then investigated the source of the oxygen in the
acetophenone product, by carrying out isotope labeling studies.
We first confirmed that the oxygen of acetophenone does not
1
8
18
exchange with H2 O under our reaction conditions. When 1- O ,
2
2+
18
prepared by reacting [Fe(TMC)] with H
2
18
(90% O-enriched,
16
O
2
1
2
8
2% H
O
2
in water), was reacted with 2-PPA under
O
2
atmosphere, we found that . 95% of oxygen in acetophenone
1
8
was derived from the O-labeled peroxo group (eqn. 4) (ESI{,
Experimental Conditions). Similarly, the reaction of 1- O ,
16
2
2
+
16
prepared by reacting [Fe(TMC)] with H
2
16
(2% H
2
O
2
O
2
in
18
18
O atmosphere (90% O-enriched)
water), with 2-PPA under
2
1
8
afforded an acetophenone product containing less than 3% O.
These results demonstrate unambiguously that the source of the
oxygen in the acetophenone product is not the molecular oxygen
4
but the peroxo group of 1.
ð4Þ
Fig. 2 Reactions of 1 with 2-phenylpropionaldehyde (2-PPA). (a) UV-
vis spectral changes of 1 (2 mM) upon addition of 2-PPA (60 equiv.,
2+
Since it has been shown very recently that [Fe(TMC)] binds
12
and activates O
2
in alcohol solvents, we attempted to generate 1
1
20 mM) at 15 uC. Inset shows absorbance traces monitored at 750 nm ($
for the reaction of 1 and m for the natural decay). (b) Plot of kobs against
-PPA concentration to determine a second-order rate constant at 15 uC.
c) Plot of first-order rate constants against 1/T to determine activation
parameters for the reaction of 1 (2 mM) and 2-PPA (60 equiv., 120 mM).
2+
by reacting [Fe(TMC)] with O
2
in the presence of 5 equiv.
triethylamine in (CH ) CHOH and observed the formation of 1
3 2
2
(
(See ESI{, Fig. S1). Interestingly, when the deformylation of
2-PPA (100 equiv., 0.2 M) was carried out in the presence of
4
530 | Chem. Commun., 2005, 4529–4531
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2
+
corresponding iron(II) species. Although we do not know the source of the
other electron at this moment, it may be suggested that one electron comes
from triethylamine present in the reaction solution.
[
Fe(TMC)] (2 mM) and triethylamine (5 equiv., 10 mM) at 25 uC
in (CH CHOH under O atmosphere, we observed a catalytic
2
3
)
2
conversion of the substrate to acetophenone and formate (20(2)
turnover number in 2 h)." In the absence of the catalyst or base,
only a small amount (, 3 TON) of acetophenone was produced
under identical conditions. Further, as we have reported previously
III
+
** The ferric-peroxo complex, [(N4Py)Fe –O ] , was prepared by a
literature method.
2
10b,10g
III
+
2
The reaction of [(N4Py)Fe –O ] (2 mM) with
40 equiv. 2-PPA at 230 uC completed within 1 min, whereas 1 did not react
with 2-PPA at 230 uC. A study of the effect of the structure of nonheme
ferric-peroxo complexes on the reactivity is currently underway in this
laboratory.
2
that the O activation depends on the structure of nonheme iron(II)
1
2
complexes, the catalytic deformylation of 2-PPA by O2 was
not observed with other nonheme iron(II) complexes such as
1 (a) D. L. Wertz and J. S. Valentine, Struct. Bonding, 2000, 97, 37; (b)
M. Sono, M. P. Roach, E. D. Coulter and J. H. Dawson, Chem. Rev.,
1996, 96, 2841; (c) P. R. Ortiz de Montellano, in Cytochrome P450:
Structure, Mechanism, and Biochemistry, ed. P. R. Ortiz de Montellano,
Plenum, New York, 1995, pp. 245–303; (d) M. Momenteau and
C. A. Reed, Chem. Rev., 1994, 94, 659.
2+
2+
[
Fe(TPA)] (TPA 5 tris(2-pyridylmethyl)amine), [Fe(N4Py)] ,
2+
and [Fe(BPMEN)]
(BPMEN 5 N,N9-dimethyl-N,N9-bis(2-
pyridylmethyl)-1,2-diaminoethane) in the presence of triethylamine
under the conditions.
2
(a) J.-J. Girerd, F. Banse and A. J. Simaan, Struct. Bonding, 2000, 97,
45; (b) M. Costas, M. P. Mehn, M. P. Jensen and L. Que, Jr., Chem.
Rev., 2004, 104, 939.
(a) M. Akhtar, M. R. Calder, D. L. Corina and J. N. Wright, J. Chem.
Soc., Chem. Commun., 1981, 129; (b) M. Akhtar, M. R. Calder,
D. L. Corina and J. N. Wright, Biochem. J., 1982, 201, 569; (c)
A. D. N. Vaz, E. S. Roberts and M. J. Coon, J. Am. Chem. Soc., 1991,
In summary, we have reported the generation and characteriza-
tion of a mononuclear nonheme ferric-peroxo complex bearing a
tetradentate N4 ligand. By using the in situ generated ferric-peroxo
intermediate directly in aldehyde deformylation reactions, we have
demonstrated that the nonheme ferric-peroxo complex is capable
of conducting aldehyde deformylation. In addition, we have
shown that the aldehyde deformylation depends on aldehyde
substrates and the ligand structure of nonheme iron ferric-peroxo
complexes. By carrying out isotope labeling studies, the source of
the oxygen in the deformylated product was shown to be the
peroxo group bound to iron. A catalytic aldehyde deformylation
by a nonheme iron(II) complex and molecular oxygen has been
demonstrated as well. Future studies will focus on attempts at
understanding mechanisms of the aldehyde deformylation by
nonheme ferric-peroxo complexes and comparing reactivities of
ferric-peroxo complexes of heme and nonheme ligands. Finally,
the present results raise the possibility that nonheme iron enzymes
may participate in aldehyde deformylation reactions, although
such enzymes/reactions have not been discovered in biological
systems yet.
1
3
113, 5886.
4
5
(a) M. Akhtar, D. L. Corina, S. Miller, A. Z. Shyadehi and J. N. Wright,
Biochemistry, 1994, 33, 4410; (b) D. C. Swinney and A. Y. Mak,
Biochemistry, 1994, 33, 2185.
(a) E. McCandlish, A. R. Miksztal, M. Nappa, A. Q. Sprenger,
J. S. Valentine, J. D. Stong and T. G. Spiro, J. Am. Chem. Soc., 1980,
1
02, 4268; (b) M. Schappacher and R. Weiss, J. Am. Chem. Soc., 1985,
107, 3736; (c) J. T. Groves and Y. Watanabe, J. Am. Chem. Soc., 1986,
08, 7834; (d) E. E. Chufan and K. D. Karlin, J. Am. Chem. Soc., 2003,
25, 16160.
1
1
6
(a) D. L. Wertz, M. F. Sisemore, M. Selke, J. Driscoll and J. S. Valentine,
J. Am. Chem. Soc., 1998, 120, 5331; (b) M. Selke and J. S. Valentine,
J. Am. Chem. Soc., 1998, 120, 2652.
7
8
Y. Goto, S. Wada, I. Morishima and Y. Watanabe, J. Inorg. Biochem.,
1
998, 69, 241.
(a) D. T. Gibson and R. E. Parales, Curr. Opin. Biotechnol., 2000, 11,
36; (b) M. D. Wolfe and J. D. Lipscomb, J. Biol. Chem., 2003, 278,
2
829; (c) A. Bassan, M. R. A. Blomberg and P. E. M. Siegbahn, J. Biol.
Inorg. Chem., 2004, 9, 439.
This work was supported by the Ministry of Science and
Technology of Korea through the Creative Research Initiative
Program.
9
A. Karlsson, J. V. Parales, R. E. Parales, D. T. Gibson, H. Eklund and
S. Ramaswamy, Science, 2003, 299, 1039.
0 (a) K. B. Jensen, C. J. McKenzie, L. P. Nielsen, J. Z. Pedersen and
1
H. M. Svendsen, Chem. Commun., 1999, 1313; (b) R. Y. N. Ho,
G. Roelfes, R. Hermant, R. Hage, B. L. Feringa and L. Que, Jr., Chem.
Commun., 1999, 2161; (c) A. J. Simaan, S. D o¨ pner, F. Banse, S. Bourcier,
G. Bouchoux, A. Boussac, P. Hildebrandt and J.-J. Girerd, Eur. J.
Inorg. Chem., 2000, 1627; (d) A. J. Simaan, F. Banse, J.-J. Girerd,
K. Wieghardt and E. Bill, Inorg. Chem., 2001, 40, 6538; (e) A. Hazell,
C. J. McKenzie, L. P. Nielsen, S. Schindler and M. Weitzer, J. Chem.
Soc., Dalton Trans., 2002, 310; (f) O. Horner, C. Jeandey, J.-L. Oddou,
P. Bonville, C. J. McKenzie and J.-M. Latour, Eur. J. Inorg. Chem.,
Notes and references
3 2 5
{ 1 was formed in alcohol solvents such as CH OH, C H OH, etc;
however, the formation and stability of 1 were different depending on the
alcohols. Since 1 showed a high stability and better spectroscopic data in
CF
in CF
It is worth noting that the reaction of 1 with other aldehydes such as
3
CH
2
OH, the characterization and kinetic studies of 1 were performed
3
CH
2
OH.
§
2002, 3278; (g) G. Roelfes, V. Vrajmasu, K. Chen, R. Y. N. Ho,
phenylacetaldehyde and 2-methyl-2-phenylpropionaldehyde was found to
depend on the structure of the aldehydes. Although a similar observation
was reported in ferric-peroxo porphyrin complex-mediated aldehyde
J.-U. Rohde, C. Zondervan, R. M. la Crois, E. P. Schudde, M. Lutz,
A. L. Spek, R. Hage, B. L. Feringa, E. M u¨ nck and L. Que, Jr., Inorg.
Chem., 2003, 42, 2639; (h) M. R. Bukowski, P. Comba, C. Limberg,
M. Merz, L. Que, Jr. and T. Wistuba, Angew. Chem., Int. Ed., 2004, 43,
1283.
7
deformylation reactions, the dependence of the reactivity of 1 on the
substrate structure is not clear at this moment and detailed investigations
are underway in this laboratory.
" The formation of 2-phenylpropionic acid, which is a product in the
oxidation of 2-phenylpropionaldehyde by oxoiron(IV) porphyrin p-cation
11 (a) H. Furutachi, K. Hashimoto, S. Nagatomo, T. Endo, S. Fujinami,
Y. Watanabe, T. Kitagawa and M. Suzuki, J. Am. Chem. Soc., 2005,
127, 4550; (b) K. Hashimoto, S. Nagatomo, S. Fujinami, H. Furutachi,
S. Ogo, M. Suzuki, A. Uehara, Y. Maeda, Y. Watanabe and
T. Kitagawa, Angew. Chem., Int. Ed., 2002, 41, 1202.
7
radicals, was not observed in this reaction. The formation of desaturation
product (i.e., styrene) was not detected either. Formate was produced in
about an equimolar amount with respect to acetophenone.
I The deformylation of 2-PAA to acetophenone and formate involves four
electrons, whereas three electrons are involved in the conversion of 1 to the
12 S. O. Kim, C. V. Sastri, M. S. Seo, J. Kim and W. Nam, J. Am. Chem.
Soc., 2005, 127, 4178.
This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 4529–4531 | 4531