Conversion of {Fe(NO)2}10 dinitrosyl iron to nitrato iron(iii) species by molecular oxygen

Article abstract of DOI:10.1039/c2dt30443k

A new {Fe(NO)₂}¹⁰ dinitrosyl iron complex possessing a 2,9-dimethyl-1,10-phenanthroline ligand has been prepared. This complex exhibits dioxygenase activity, converting NO to nitrate (NO₃ ^-) anions. During the o

Full text of DOI:10.1039/c2dt30443k

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COMMUNICATION
Conversion of {Fe(NO)2}10 dinitrosyl iron to nitrato iron(III) species by
molecular oxygen†
Kelsey M. Skodje, Paul G. Williard and Eunsuk Kim*
Received 23rd February 2012, Accepted 3rd April 2012
DOI: 10.1039/c2dt30443k
A new {Fe(NO)2}10 dinitrosyl iron complex possessing a 2,9-
dimethyl-1,10-phenanthroline ligand has been prepared.
This complex exhibits dioxygenase activity, converting NO to
nitrate (NO3−) anions. During the oxygenation reaction, for-
mation of reactive nitrating species is implicated, as shown in
the effective o-nitration with a phenolic substrate.
Cellular non-heme iron species, such as iron–sulfur clusters,
Fig. 1 {Fe(NO)2}10 dinitrosyl iron complexes (DNICs).
react with nitric oxide to form dinitrosyl iron complexes
(DNICs).1,2 EPR active, cysteine-bound DNICs, formulated as
[Fe(NO)2(SR)2]−, {Fe(NO)2}9 species in the Enemark–Feltham
notation,3 were the first to be discovered.4–6 Though S-bound
of [Fe(dmp)(NO)2] (1) along with the characterization of its oxy-
genation product, [Fe2O(NO3)4(dmp)2] (2).
Compound 1 was synthesized from the reaction between
{Fe(NO)2}9 DNICs are more common, N- or O-bound varieties
have been observed in nature,7–10 and a series of S-, N-, or
C-bound synthetic DNICs have been reported.1,11,12
Fe(CO)2(NO)2 and dmp in a manner similar to how other
1
{Fe(NO)2}10 DNICs have been prepared.12o The H NMR spec-
Physiological roles such as involvement in the storage and
transfer of NO have been suggested for DNICs.1,2,13 In addition,
trum of 1 exhibits well-resolved dmp hydrogen resonances with
we have recently demonstrated unprecedented dioxygen reactiv-
ity of an N-bound {Fe(NO)2}10 DNIC, [Fe(TMEDA)(NO)2]
(Fig. 1), in which an intermediate is formed that leads to the
nitration of phenol.14 This intermediate is stable below −80 °C,
allowing us to spectroscopically characterize it and propose it as
little changes in the chemical shift compared to those of free
dmp, indicative of a diamagnetic complex. The IR spectrum of 1
in KBr shows NO stretching frequencies at 1628 and 1692 cm−1
which are comparable to those (1628 and 1686 cm−1) of
[Fe(TMEDA)(NO)2]. The reversible {Fe(NO)2}9/10 redox behav-
ior of 1 in dichloromethane was studied by cyclic voltammetry,
a
putative iron–peroxynitrite species, [Fe(TMEDA)(NO)-
(ONOO)].14 Despite our success in characterizing the low-temp-
erature-stable intermediate, we had previously been unable to
glean any information from its room temperature decomposition
product(s). Warming the intermediate above −80 °C, as well as
reacting [Fe(TMEDA)(NO)2] with O2 at room temperature,
resulted in a reddish, insoluble precipitate, which hampered
further characterization.14 In our effort to seek the final room-
temperature-stable product(s) derived from the putative iron–per-
oxynitrite intermediate, we have prepared a new {Fe(NO)2}10
DNIC utilizing a rigid dmp ligand, where dmp = 2,9-dimethyl-
1,10-phenanthroline (Fig. 1). The change of the coordinating
ligand from TMEDA to dmp finally led us to characterize the
room-temperature-stable reaction product of an {Fe(NO)2}10
DNIC with O2. Here, we report the synthesis and O2 reactivity
+ 15
with E1/2 = −0.402 V vs. FeCp2/FeCp2 , indicating that 1 is
harder to oxidize than [Fe(TMEDA)(NO)2] which possesses an
E
1/2 of −0.510 V under the same experimental conditions.
The reaction between 1 and O2 is much slower compared to
that of [Fe(TMEDA)(NO)2]/O2. The complete oxygenation of 1
requires a few minutes in solution at room temperature
whereas that for [Fe(TMEDA)(NO)2] is instant. At low tempera-
tures (e.g., −80 °C), a putative peroxynitrite intermediate,
[Fe(TMEDA)(NO)(ONOO)], is generated from [Fe(TMEDA)-
(NO)2]/O2,14 while no such species is observed with 1/O2.
Despite its rather sluggish reactivity towards O2, 1 in the pres-
ence of O2 does effectively nitrate phenol similarly to
[Fe(TMEDA)(NO)2]. When excess O2 is added to a solution of
[Fe(dmp)(NO)2] (1) and one equivalent of 2,4-di-t-butylphenol
(DBP), 65% of the DBP is converted to 2,4-di-t-butyl-6-nitro-
phenol (NO2-DBP), Scheme 1. The yield of NO2-DBP formation
by 1/O2 is comparable to that (58%) obtained by [Fe(TMEDA)-
(NO)2]/O2 under identical experimental conditions.14 This
common reactivity implies that the phenol nitration chemistry
observed with 1/O2 and [Fe(TMEDA)(NO)2]/O2 may share a
common mechanism in which an iron–peroxynitrite species
plays a critical role.
Department of Chemistry, Brown University, Providence, RI 02912,
USA. E-mail: eunsuk_kim@brown.edu
†Electronic supplementary information (ESI) available: Experimental
procedures as well as a CIF file giving X-ray crystallographic data for
complex 2. CCDC XXXXXX. For ESI and crystallographic data in CIF
or other electronic format see DOI: 10.1039/c2dt30443k
This journal is © The Royal Society of Chemistry 2012
Dalton Trans., 2012, 41, 7849–7851 | 7849

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Scheme 1 Nitration of phenol by [Fe(dmp)(NO)2] (1) and O2.
Fig. 2 ORTEP drawing of 2 with 50% thermal ellipsoids. Hydrogen
atoms were omitted for clarity. Selected bond distances (Å) and angles
(°) are as follows: Fe(1)–O(1) 1.772, Fe(1)–O(2) 2.238, Fe(1)–O(3)
2.150, Fe(1)–O(5) 2.193, Fe(1)–O(6) 2.127, Fe(1)–N(1) 2.127, Fe(1)–
N(2) 2.220, N(3)–O(2) 1.252, N(3)–O(3) 1.256, N(3)–O(4) 1.176,
N(4)–O(5) 1.260, N(4)–O(6) 1.265, N(4)–O(7) 1.203, Fe(1)–O(1)–Fe(1)
144.58, O(1)–Fe(1)–O(2) 90.46, O(1)–Fe(1)–O(3) 90.72, O(1)–Fe(1)–
O(5) 97.77, O(1)–Fe(1)–O(6) 94.70, O(1)–Fe(1)–N(1) 102.99, O(1)–
Fe(1)–N(2) 170.85, O(2)–Fe(1)–O(3) 57.96, O(5)–Fe(1)–O(6) 58.71,
O(2)–Fe(1)–O(5) 155.75, O(3)–Fe(1)–N(1) 132.60, O(6)–Fe(1)–N(1)
136.38, N(1)–Fe(1)–N(2) 77.42, Fe⋯Fe 3.375.
Scheme 2 Oxygenation of [Fe(dmp)(NO)2] (1) in the absence of
phenol.
In the absence of the phenolic substrate such as DBP, one
would expect that the unstable iron–peroxynitrite moiety may
isomerize to thermally stable iron–nitrato species at room temp-
erature, as has been seen with metal-bound peroxynitrite found
in the literature.16 Although we did not observe the formation of
an iron–peroxynitrite intermediate from 1/O2, we did obtain a
thermally stable iron–nitrato complex as a final reaction product.
When 1 was reacted with 3 equivalents of O2 at room tempera-
ture in acetonitrile, an oxo bridged dinuclear iron(III)–nitrato
complex, [Fe2O(NO3)4(dmp)2] (2) (Scheme 2), was formed as a
black crystalline solid whose structure was determined by X-ray
crystallography (vide infra). The crystals of 2 are stable in air but
2 in a non-crystalline form is not. If left in air, 2 gradually
decomposes to the reddish, nitrate containing insoluble precipi-
tate, similar to what was observed in previous [Fe(TMEDA)-
(NO)2]/O2 reactions. Compound 2 itself is incapable of nitrating
DBP to NO2-DBP, suggesting that the reactive nitrating species,
a putative iron–peroxynitrite, must be generated prior to the for-
mation of 2.
The crystal structure of 2 (Fig. 2) reveals a dinuclear iron(III)
center in which two ferric ions are singly bridged by a μ-oxo
ligand.17 The bridging oxo atom lies on a crystallographic 2-fold
axis of symmetry.18 Each iron center is seven-coordinate with an
oxo bridge, one dmp, and two nitrato chelates derived from its
original NO ligand. The geometry of each iron center can be
described as distorted pentagonal bipyramidal with axial ligands
provided by dmp and the μ-oxo moiety. The nitrato chelates are
asymmetrically bound to iron, in which some of the Fe–O-
(nitrato) bonds, Fe–O2 (2.238 Å) and Fe–O5 (2.193 Å), are
notably elongated with respect to the others. The short Fe–O1-
(oxo) distance of 1.772 Å is characteristic of the diferric Fe–O–
Fe unit and the Fe–O–Fe angle of 144.58° is in the range for
typical (μ-oxo)diiron(III) compounds.19 There are a few structural
analogs that share the (μ-oxo)tetrakis(nitrato) diiron(III) feature
such as [Fe2O(NO3)4(bpy)2] and [Fe2O(NO3)4(C7H7N3)4],20,21
although they were prepared through completely different
synthetic methods. Interestingly, with the very related phen
ligand, where phen = 1,10-phenanthroline, the aquo analog,
[Fe2O(H2O)6(phen)2](NO3)4, is known,22 in which nitrate serves
as a counter anion instead of a coordinating ligand. This com-
pound has been synthesized from the aqueous solution as a
stable entity and crystallographically characterized. It is likely
that the coordinated nitrato ligand in 2 is susceptible to ligand
substitution by water, which may explain the decomposition of 2
in the presence of excess water (vide infra).
The IR spectrum of 2 shows characteristic bands for bound
nitrato ligands at 1286 and 1510 cm−1, which closely match the
known IR features of the iron(III)–nitrato complexes23,24 and are
drastically different from that (1383 cm−1) of free nitrate. The
antisymmetric Fe–O–Fe stretch (νas) occurs at 812 cm−1, consist-
ent with the μ-oxo bridged crystal structure. The oxo bridge of 2
comes from molecular oxygen. With 2 prepared with 18O2, we
observe the shifted νas(Fe–O–Fe) at 774 cm−1 (Δνas
=
38 cm−1).25 However, this oxo group is also exchangeable with
water in solvent during the formation of 2. When we carried out
the 1/O2 reaction in the presence of a small quantity (10 eq.) of
H218O, we observed both the 18O-labeled and unlabeled νas(Fe–
O–Fe) frequencies in the IR spectrum. Too much excess water
hinders the formation of 2 and only the reddish insoluble solid
can be obtained from 1/O2.
Nitration of phenolic substrates such as tyrosine is important
in biology because such a modification is often observed in
many disease conditions.26,27 The present work as well as our
previous report14 have shown that {Fe(NO)2}10 DNICs are
capable of facilitating such chemistry, suggesting a possible new
physiological role for the cellular DNICs. Characterization of
compound 2 in this report further supports our proposal on the
formation of iron–peroxynitrite species from {Fe(NO)2}10 and
O2 because peroxynitrite, if formed, is expected to isomerize to
thermally stable nitrate at room temperature in the dark.16,28
In fact, the conversion of dinitrosyl iron to an iron–nitrato
7850 | Dalton Trans., 2012, 41, 7849–7851
This journal is © The Royal Society of Chemistry 2012

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species by O2 had been observed as early as the 1980s by Postel
and coworkers.29 Although neither the formation of peroxynitrite
nor phenol nitration chemistry were investigated by Postel, oxi-
dation of substrates such as phosphines and olefins was reported
during the oxygenation.29 Since we now learn that peroxynitrite
can be generated from DNICs and O2, it would be worth revisit-
ing Postel’s system to probe the involvement of peroxynitrite and
test the generality of such a reaction.
In summary, we have reported a new {Fe(NO)2}10 dinitrosyl
complex [Fe(dmp)(NO)2] (1) that facilitates nitration of phenol
in the presence of O2. In the absence of phenolic substrates, oxy-
genation of 1 leads to the formation of a nitrato compound,
[Fe2O(NO3)4(dmp)2] (2), which itself is incapable of nitrating
phenols, indicating that a reactive nitrating species forms prior to
the formation of 2. We suggest that a peroxynitrite (ONOO−)
species, which is a powerful nitrating agent and is known to iso-
merize to nitrate (NO3−), is involved in the nitration reactivity
of 1/O2.
13 D. R. Richardson and H. C. Lok, Biochim. Biophys. Acta, 2008, 1780,
638.
14 N. G. Tran, H. Kalyvas, K. M. Skodje, T. Hayashi, P. Moenne-Loccoz,
P. E. Callan, J. Shearer, L. J. Kirschenbaum and E. Kim, J. Am. Chem.
Soc., 2011, 133, 1184.
15 This value falls within the expected range for neutral N-bound DNICs.
See ref. 12h and 12o as well asN. Reginato, C. T. C. McCrory,
D. Pervitsky and L. J. Li, J. Am. Chem. Soc., 1999, 121, 10217;
R. E. Dessy, J. C. Charkoud and A. L. Rheingold, J. Am. Chem. Soc.,
1972, 94, 738.
Acknowledgements
The authors thank Brown University (E.K.), the Camille and
Henry Dreyfus New Faculty Award Program (E.K.), and the
NSF (P.G.W. 1058051) for financial support.
16 S. Goldstein, J. Lind and G. Merenyi, Chem. Rev., 2005, 105, 2457.
17 C15H13.50FeN4.50O6.50, M = 416.65, monoclinic, a = 17.72(3) Å, b =
12.90(2) Å, c = 14.74(3) Å, U = 3359.00(11) Å3, T = 173(2) K, space
group C12/c1, Z = 8, μ = 0.945 mm−1, reflections collected = 13 820,
3314 unique (Rint = 0.0687) which were used in all calculations. The
final wR(F2) was 1.044 (all data).
18 This crystal also incorporates a molecule of acetonitrile not shown in
Fig. 2 whose linear axis also lies on a crystallographic 2-fold axis of
symmetry.
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This journal is © The Royal Society of Chemistry 2012
Dalton Trans., 2012, 41, 7849–7851 | 7851