Unexpected NO transfer reaction between trans -[RuII(NO +)(NH3)4(L)]3+ and Fe(III) species: Observation of a heterobimetallic no-bridged intermediate

Article abstract of DOI:10.1021/ic500122b

The reaction between trans-[Ru^II(NO⁺)(NH ₃)₄(L)]³⁺, L = ImN, IsN, Nic, P(OMe) ₃, P(OEt)₃, and P(OH)(OEt)₂, and the Fe(III) species [Fe^III(TPPS)], metmyoglobin, and hemoglobin was monitored by UV-vis, EPR, and electrochemical techniques (DPV, CV). No reaction was observed when L = ImN, IsN, Nic, and P(OH)(OEt)₂. However, when L = P(OMe)₃ and P(OEt)₃, the reaction was quantitative and the products were trans-[Ru^III(H₂O)(NH₃) ₄(P(OR)₃)]³⁺ and [Fe^II(NO ⁺)] species. Reaction kinetics data and DFT calculations suggest a two-step reaction mechanism with the initial formation of a bridged [Ru-(μNO)-Fe] intermediate, which was confirmed through electrochemical techniques (E⁰′ = -0.47 V vs NHE). The calculated specific rate constant values for the reaction were in the ranges k₁ = 1.1 to 7.7 L mol^-1 s^-1 and k₂ = 2.4 × 10 ^-3 to 11.4 × 10^-3 s^-1 for L = P(OMe) ₃ and P(OEt)₃. The oxidation of the ruthenium center (Ru(II) to Ru(III)) containing the nitrosonium ligand suggests that NO can act as an electron transfer bridge between the two metal centers.

Full text of DOI:10.1021/ic500122b

Article
pubs.acs.org/IC
Unexpected NO Transfer Reaction between trans-
[RuII(NO+)(NH3)4(L)]3+ and Fe(III) Species: Observation of a
Heterobimetallic NO-Bridged Intermediate
Gustavo Metzker,† Pietro P. Lopes,†,‡ Augusto C. H. da Silva,† Sebastiao C. da Silva,§
and Douglas W. Franco*,†
†Instituto de Química de Sao Carlos, Universidade de Sao Paulo, Avenida Trab. Sao-Carlense 400, Sao Carlos, SP, Brazil
̃
̃
̃
̃
‡Argonne National Laboratory, 9700 S Cass Avenue, Lemont, Illinois, United States
§Universidade Federal de Mato Grosso, Avenida Fernando Correa
da Costa 2367, Cuiaba, MS, Brazil
̂
S
* Supporting Information
ABSTRACT: The reaction between trans-[RuII(NO+)(NH3)4(L)]3+, L =
ImN, IsN, Nic, P(OMe)3, P(OEt)3, and P(OH)(OEt)2, and the Fe(III) species
[FeIII(TPPS)], metmyoglobin, and hemoglobin was monitored by UV−vis,
EPR, and electrochemical techniques (DPV, CV). No reaction was observed
when L = ImN, IsN, Nic, and P(OH)(OEt)2. However, when L = P(OMe)3
and P(OEt)3, the reaction was quantitative and the products were trans-
[RuIII(H2O)(NH3)4(P(OR)3)]3+ and [FeII(NO+)] species. Reaction kinetics
data and DFT calculations suggest a two-step reaction mechanism with the
initial formation of a bridged [Ru−(μNO)−Fe] intermediate, which was
confirmed through electrochemical techniques (E0′ = −0.47 V vs NHE). The
calculated specific rate constant values for the reaction were in the ranges k1 =
1.1 to 7.7 L mol−1 s−1 and k2 = 2.4 × 10−3 to 11.4 × 10−3 s−1 for L = P(OMe)3
and P(OEt)3. The oxidation of the ruthenium center (Ru(II) to Ru(III))
containing the nitrosonium ligand suggests that NO can act as an electron transfer bridge between the two metal centers.
Metmyoglobin is used as a spectrophotometric probe to
detect nitroxyl formation owing to the ability of HNO to
reduce the iron(III) center.20 During experiments examining
the possible generation of HNO from trans-[RuII(NO+)-
(NH3)4(P(OEt)3)]3+, myoglobin was used as an HNO trap.1
A significant change was observed in the myoglobin spectrum
simply by mixing the above ruthenium nitrosyl and the
myoglobin.
In order to verify the possibility that iron(III) nitrosylation
occurs without requiring a nitrosonium activation pathway, we
investigated the NO transfer reaction between the iron(III)
species [FeIII(H2O)TPPS], metmyoglobin, and hemoglobin
and ruthenium nitrosyl complexes trans-[RuII(NO+)-
(NH3)4(L)]3+. We interpret this reaction as an unprecedented
example of an inner-sphere electron transfer process through an
NO bridge.
INTRODUCTION
■
Ruthenium nitrosyl complexes, trans-[RuII(NO+)(NH3)4(L)]-
(X)n, are able to deliver nitric oxide (NO) or nitroxyl (HNO),
in vitro and in vivo, after one- or two-electron reductions,1−8
which are the key steps for the biological action of this class of
compounds. Iron-containing proteins,9 such as soluble guanylyl
cyclase,10 and thiol proteins11 are the probable targets of these
nitrogen oxides and result in various physiological effects.12
Nitrosylation reactions with metalloproteins are important in
nitrogen oxide biology and can occur via NO transfer between
two metal centers. There are two proposed different pathways
for this reaction (eqs 1/2 and eqs 3/4):13−19
EXPERIMENTAL SECTION
■
Reagents and Synthesis. Ruthenium(III) chloride hydrate
(Strem Chemicals), hydrazine monohydrate 99% (Sigma-Aldrich),
hydrochloric acid 37% (Aldrich), trifluoroacetic acid 99% (Sigma-
Aldrich), zinc ≥99.9% (Aldrich) and mercury 99.99% (Sigma-Aldrich)
to prepare zinc amalgam, sodium nitrite 99% (Sigma-Aldrich),
In both mechanisms, there is no electron transfer between
the two metal centers during the reaction. Also, NO instead of
nitrosonium (NO+) is involved in the reactions. Kinetics, DFT
calculations, and binuclear identification data involving this type
of reaction are scarce.
Received: January 17, 2014
Published: April 16, 2014
© 2014 American Chemical Society
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Figure 1. Spectral changes during the reaction of iron(III) species with the trans-[RuII(NO+)(NH3)4(P(OEt)3)]3+ ion in aqueous solution. (A) CRu
= 6.0 × 10−5 mol L−1; C[Fe = 3.0 × 10−6 mol L−1; (B) CRu = 8.0 × 10−4 mol L−1; CmetMb = 4.0 × 10−5 mol L−1. T = 25.0 0.1 °C.
IIITPPS]
ammonium hexafluorophosphate 99% (Strem Chemicals), imidazole
99% (Aldrich), isonicotinamide 99% (Aldrich), nicotinamide 98%
(Sigma), and diethyl phosphite 98% (Aldrich) were used as received.
Trimethyl and triethyl phosphite 98% (Sigma-Aldrich) were treated
with metallic sodium, distilled under vacuum, and ampuled (1.0 mL)
under an argon atmosphere. The reagents iron sulfate heptahydrate
(Merck), 4,4′,4″,4‴-(porphine-5,10,15,20-tetrayl)tetrakis-
(benzenesulfonic acid) tetrasodium salt hydrate (TPPS, Aldrich),
Dowex 50WX8-200 (Sigma-Aldrich), and acetone and methanol
HPLC grade (Panreac) were used as received. The complexes trans-
[RuII(NO+)(NH3)4(L)](X)3 and its synthetic precursors were
synthesized as described before.21−26 The [FeIII(Cl)(TPPS)] synthetic
procedure followed the literature.27
galvanostat (Princeton, USA). A three-electrode systema glassy
carbon or a PAR static mercury drop electrode (SMDE), model 303A,
as working electrodes, platinum plate as auxiliary electrode, and a
saturated calomel electrode as referencewas used. All potentials
reported are converted to the normal hydrogen electrode (NHE). The
NO detection in solution was carried out by an electrochemical
apparatus from Innovative Instruments, model inNO-T, coupled with
an amino 700 electrode (maximum electrode response: 200pA/nmol
of NO). The detection limit determined in the experimental
conditions utilized was 5.0 × 10−7 mol L−1 of NO.
Kinetics Treatment. The kinetic analysis was performed using a
reaction model based on a two-step reaction, described in detail in the
Supporting Information. The absorbance curves were normalized to
simplify the fitting procedure.
Experimental Procedures. All solutions were prepared using
high-purity water (Milli-Q system, Bedford, MA, USA). Solutions of
trifluoroacetic acid (pH = 4.0; μ = 0.1 mol L−1 CF3COOH/
CF3COONa) were used in all experiments, unless otherwise
mentioned. The temperature was always kept at 25.0 0.1 °C. All
manipulations were performed in an inert atmosphere using high-
purity argon or using a Schlenk line by the freeze−pump−thaw
method.27 Argon was purified by passing it through a washing flask
containing Cr(II) in acidic medium and then in a second vessel
containing concentrated sulfuric acid.28 After this treatment, the
residual oxygen in the gas was lower than 10 ppb.28 Myoglobin from
equine skeletal muscle (Sigma) and human hemoglobin (Sigma) were
purified by passing its solutions through a glass column (1.0 × 10.0
cm) filled with Sephadex G-25 (Sigma) as solid phase.29 The
previously mentioned trifluoroacetic acid solutions were used as
eluent. The protein concentration in the solution was determined by
DFT Calculations. Molecular optimizations by DFT33 were carried
out using a Gaussian 03 package34 with the B3LYP exchange−
correlation function.35,36 The Density Gauss Double-Zeta Valence
Polarized basis set37−39 (DGDZVP) was used for all atoms. All
calculations were performed using the IEPCM solvation method.40−42
The transition-state structures were optimized using the QST3
without freezing the molecular coordinates.
RESULTS
■
Product and Stoichiometry Analysis: Reactions of
trans-[RuII(NO+)(NH3)4(L)]3+ with [FeIII(Cl)TPPS] and Met-
myoglobin. The reaction of trans-[RuII(NO+)(NH3)4(L)]3+
with [FeIII(Cl)TPPS] and metmyoglobin referred to herein as
[FeIIITPPS] and metMb, respectively, was followed using UV−
vis spectroscopy. When L = ImN, IsN, Nic, and P(OH)(OEt)2,
no reaction was observed even with a large excess (150-fold
excess over the iron(III) species) of the ruthenium complexes.
However, when L = P(OEt)3 and P(OMe)3, the reaction
occurred immediately. Figure 1A and B show the progress of
the reactions of trans-[RuII(NO+)(NH3)4(P(OEt)3)]3+ with
[FeIIITPPS] and with metMb in aqueous solution. During the
course of the reaction new bands were observed at 420/538 nm
for [FeIIITPPS] (Figure 1A (I)), with isosbestic points at 407,
460, and 529 nm. For metMb, the new bands were observed at
535/570 nm (Figure 1B (I)) with isosbestic points at 482, 518,
and 598 nm. The band maxima (420, 533 and 535, 570 nm)
correspond to the iron(II) nitrosyl {FeII(NO+)}6 formation.32
The same behavior was observed for the reaction between
human hemoglobin and trans-[RuII(NO+)(NH3)4(P(OEt)3)]3+
(Supporting Information, Figure S1). Also, following the
reaction in the presence of selective NO electrode, it was not
possible to observe the presence of free NO in the solution.
UV−vis spectroscopy (myoglobin: λ = 502 nm, ε = 9.5 × 103 L mol−1
30
cm−1
;
hemoglobin: λ = 530 nm, ε = 1.0 × 104 L mol−1 cm−1 31).
Solutions of [FeIII(Cl)TPPS] were prepared by dissolving the required
amount of solid in the previously mentioned trifluoroacetic acid
solution, and the concentration was checked using the UV−vis
spectrum (λ = 392 nm; ε = 1.55 × 105 L mol−1 cm−1).32 Electronic
spectra were obtained on a Hitachi U3501 spectrophotometer (Tokyo,
Japan) or on a Thermo Multiskan GO (Vantaa, Finland)
spectrophotometer using a 1.00 cm path length quartz cell. For the
measurements in an inert atmosphere, a high-vacuum glass stopcock
was adapted to the cuvette. Electron paramagnetic resonance spectra
were obtained using a Bruker EMX Plus spectrometer (Rheinstetten,
Germany) coupled with a standard or cylindrical cavity operating in
the X-band. The reaction progress was followed by electron
paramagnetic resonance spectroscopy (EPR) by transferring aliquots
of a stock aqueous solution where the reaction was taking place
directly in a previously deaerated 4 mm quartz EPR tube (Wilmad
Labglass, USA). The spectra were recorded at −196 °C (N2(l)) or
−263 °C (He(l)). For field calibration, a capillary tube containing
DPPH• was used. Cyclic voltammetry (CV) and differential pulse
voltammetry (DPV) were performed in a PAR 264A potentiostat/
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The reaction was also followed by electron paramagnetic
resonance spectroscopy for detecting the formation of a
paramagnetic species with g = 2.42, as exemplified in Figure
2, whose spectrum matches with the one previously reported
Figure 3. Time dependency absorption profile for the reaction of
[FeIIITPPS] with the trans-[RuII(NO+)(NH3)4(P(OEt)3)]3+ ion in
−1
= 3.0 × 10−6 mol L . Ratio Fe:Ru ( )
IIITPPS]
■
aqueous solution. C[Fe
●
▲
▼
1:10; ( ) 1:20; ( ) 1:30; ( ) 1:40. Curves correspond to the
formation of [FeII(NO+)TPPS] at λ = 420 nm.
trans‐[RuII(NO+)(NH3)4(P(OR)3)]3+ + [FeIII(L)]
→ [(P(OR)3)(NH3)4RuII(μ‐NO+)FeIII(L)]n
Figure 2. EPR spectra showing trans-[RuIII(H2O)(NH3)4(P(OEt)3)]3+
formation during the reaction between trans-[RuII(NO+)(NH3)4(P-
k1
(6)
(OEt)3)]3+ and [FeIIITPPS]. CRu = 1.5 × 10−3 mol L−1; C[Fe
=
IIITPPS]
7.5 × 10−5 mol L−1; T = −196 °C. Microwave frequency: 9.4559 GHz.
The g⊥ = 1.72 was not observed by its intrinsic small intensity in the
EPR spectrum and for the small concentration of Ru(III) formed
during the reaction.
[(P(OR)3)(NH3)4RuII(μ‐NO+)FeIII(L)]n
k2
→ trans ‐[ RuIII(H2O)(NH3)4(P(OR)3)]3+
+ [FeIII(NO+)]
(7)
Using the expressions described in the Supporting
Information, the specific rate constants (k1, k2) listed in
Table 1 were calculated.
for trans-[RuIII(H2O)(NH3)4(P(OEt)3)]3+.43 Since the concen-
tration of Ru(III) formed is in the range 10−5 mol L−1, the
signal−noise relation of the spectra is small, with the
identification of the g⊥ = 1.72 becoming impracticable. Thus,
to confirm the formation of the Ru(III) species, CV
a
Table 1. Calculated Specific Rate Constants for the
Reaction between trans-[RuII(NO+)(NH3)4(L)]3+ and
experiments were conducted and an anodic peak at E0′Ru
Iron(III) Species
III/RuII
= 0.70 V24 was observed, matching with the formation of the
trans-[RuIII(H2O)(NH3)4(P(OEt)3)]3+ complex (Figure S2,
Supporting Information). A similar behavior was observed
when L = P(OMe)3.
b
L
[FeIII(L)]
k1 (L mol−1 s−1
)
k2 (s−1
)
P(OMe)3
TPPS
metMb
TPPS
metMb
Hb
7.7 0.5
1.1 0.1
2.8 0.1
2.1 0.1
2.4 0.2
(2.7 0.1) × 10−3
(5.3 0.10 × 10−3
(2.4 0.4) × 10−3
(11.4 0.5) × 10−3
(8.5 0.5) × 10−3
P(OEt)3
The quantification of the [FeII(NO+)] species ([FeII(NO+)-
TPPS]: λmax = 420 nm/ε = 2.56 × 105 L mol−1 cm−1;
[MbFeII(NO+)]: λmax = 536 nm/ε = 9.0 × 103 L mol−1 cm−1)32
and the quantitative conversion of trans-[RuII(NO+)(NH3)4(P-
(OEt)3)]3+ into trans-[RuIII(H2O)(NH3)4(P(OEt)3)]3+
strongly suggest that the following overall reaction has
occurred:
a
T = 25.0 0.1 °C, pH = 4.0 (CF3COOH/CF3COONa; μ = 0.1 mol
b
L−1). For L = P(OH)(OEt)2, ImN, IsN, and Nic no reaction was
observed.
The thermodynamic activation parameters of the reaction
between [FeIIITPPS] and trans-[RuII(NO+)(NH3)4(P-
(OEt)3)]3+ were calculated using the Eyring equation (Tables
S1 and S2 and Figure S3, Supporting Information). For the first
(k1) and second (k2) reaction steps the activation parameter
values found were respectively ΔH⧧ = 104.9/70.3 kJ mol−1,
ΔS⧧ = 144.8/−57.7 J mol−1 K−1, and ΔG⧧ = 61.1/87.4 kJ
mol−1.
trans‐[RuII(NO+)(NH3)4(P(OR)3)]3+ + [FeIII(L)]
→ trans‐[RuIII(H2O)(NH3)4(P(OR)3)]3+
+ [FeII(NO+)]
(5)
Kinetic Analysis, Proposed Mechanism, and Thermo-
dynamics. A sigmoidal curve was obtained by plotting
absorbance corresponding to the formation of the
{FeII(NO+)}6 species versus time, suggesting the formation of
intermediate species,44,45 Figure 3.
Identification of the Binuclear Intermediate. Following
the reaction between [FeIIITPPS] and trans-[RuII(NO+)-
(NH3)4(P(OEt)3)]3+ by electrochemical techniques (CV and
Based on the absorbance profile above, and taking in account
the reported data in the literature for binuclear compounds
with a bridging NO ligand,13−19 the following reaction scheme
was proposed (eqs 6 and 7):
DPV), two new cathodic waves, Ecp1 = −0.47 V and Ecp2 =
−0.35 V, Figure 4A, appeared in the voltammetric spectra
during the course of the reaction. It is important to emphasize
that theses peaks were not present at the beginning of the
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Figure 4. (A) DPV curves obtained using the SMDE electrode of the reaction between [FeIIITPPS] and trans-[RuII(NO+)(NH3)4(P(OEt)3)]3+.
Solid line (black): binuclear formation and decay; dashed line (red): product formation. CRu = 7.15 × 10−4 mol L−1; C[Fe TPPS] = 7.15 × 10−5 mol
III
L−1; T = 25.0 0.1 °C. (B) Plot of normalized current versus time using the DPV data.
reaction. The current−time profile for the Ecp1 showed a
behavior compatible with the one exhibited for the formation
and decay of the proposed binuclear species (Figure 4B, black
line). Also, the electrochemical process (Ecp1) was shown to be
irreversible. The potential window in which these electro-
chemical processes were observed is distant from the redox
in the porphyrin ring, while HOMO−2 is concentrated
predominantly on the NO ligand (46%). Table S3 also shows
that the composition of HOMO−12 (Fe: 11%; NO: 2%; Ru:
51%; TPPS: 5%; NH3: 2%; P(OEt)3: 29%) is delocalized along
the [Ru−(μNO)−Fe] axis, representing a ligand interaction,
coherently with the formation of the binuclear species.
With regard to LUMO and LUMO+1 orbitals, the main
contribution of their composition is centered in the NO ligand
(17% and 80%, respectively), which predicts that reduction of
the binuclear species, as observed in Figure 4, would probably
occur in this fragment. This observation reinforces the
hypothesis that the ECP1 peak observed in the DPV corresponds
to the electrochemical process presented in eq 8. Also, the
slight energy difference between the LUMO and LUMO+1
orbitals (0.9 kcal mol−1) indicates they are nearly degenerate.
Figure S4 (Supporting Information) shows the optimized
structure for the binuclear complex and the density plots of the
orbitals discussed above.
couples for [FeIII(H2O)TPPS] (E0′Fe
= 0.014 V),27 trans-
+ 0
III/FeII
[RuII(NO+)(NH3)4(P(OEt)3)]3+/2+ (E0′NO /NO = 0.11 V),2 or
trans-[RuIII(H2O)(NH3)4(P(OEt)3)]3+/2+ (E0′Ru
= 0.70
III/RuII
V).24 Therefore, the Ecp1 process was tentatively interpreted
as one-electron reduction of the heterobinuclear complex, eq 8.
[(P(OR)3)(NH3)4RuII(μ‐NO)FeIII(L)]n
1e−
⎯⎯→ [(P(OR)3)(NH3)4RuII(μ‐NO)FeIII(L)](n−1)
(8)
By plotting the peak current of peak Ecp2 versus time (Figure
4 B, red curve) a sigmoidal behavior was observed for the
product formation, which is similar to the one shown in Figure
3. As reported by Meyer,27 the reduction potential for the
[FeII(NO0)TPPS]4−/[FeII(NO−)TPPS]5− couple is E0′ =
−0.38 V. Since different experimental conditions could
probably account for the 0.030 V difference between the
values observed here (E0′ = −0.35 V) and the one reported in
the literature, the peaks (III) and (IV) were attributed to the
[FeII(NO0)TPPS]4−/[FeII(NO−)TPPS]5− electrochemical
process. The formation of [FeII(NO+)TPPS] was confirmed
by UV−vis, providing additional support to the above assertion.
The identification of the intermediate by its UV−vis
spectrum was also attempted, but without conclusive results.
By trying to extract the spectrum for any intermediate formed
during the time scale of the reaction, taking into account both
reagents and products, it was still not possible to observe any
new band in the resulting spectrum. Using TD-DFT for the
optimized structure of the intermediate it was observed that the
proposed intermediate would exhibit an absorption band at UV,
but with a molar absorptivity compared with the iron(III)
species. These overlapping bands would be coherent with the
nonobservation of intermediate species when following the
reaction by absorption spectroscopy.
DISCUSSION
■
Since the complexes trans-[RuII(NO+)(NH3)4(L)]n+ only
liberate NO in solution after a one-electron reduction, with
specific rate constants ranging from 2.5 × 10−2 (L = IsN) to
0.98 s−1 (L= P(OEt)3), the spontaneous dissociation of NO is
unlikely to occur due to the nitrosonium characteristic of the
NO ligand in these complexes.2 Therefore, taking into account
the experimental data of Table 1 and the accumulated kinetic
data of the ruthenium and iron species, the reaction mechanism
described by eqs 1 and 2 is unlikely to occur. Thus, it is quite
reasonable to assume that the reaction observed between the
ruthenium nitrosyl complexes and iron(III) species takes place
through the mechanism described by eqs 3 and 4.
The nature of the ligand trans positioned to NO+ in the
ruthenium nitrosyl complexes proved to be important in the
reactivity of these complexes. As observed, the reaction occurs
only when the phosphorus esters P(OMe)3 and P(OEt)3, but
not P(OH)(OEt)2, are present in the coordination sphere.
These phosphorus ligands exhibit the highest π-acidity among
all the other ligands dealt with in this work.2,48 The higher the
π-acidity of the NO trans ligand, the more electrophilic is the
The formation of a possible binuclear complex was also
investigated using DFT calculations. The structure of the
intermediate was optimized with NO as a bridging ligand.
Taking into account the composition of the molecular orbitals
presented in Table S3 (Supporting Information), it can be
observed that the HOMO and HOMO−1 orbitals are centered
NO ligand (observed by ν(NO+) and E0′NO /NO values in
Table S4), and therefore, the easier it is for the reaction to
occur.
+
0
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The values of k1 and k2 for the reaction between the iron(III)
species and ruthenium nitrosyls are similar, even when
considering the structural differences between the heme
proteins and the [FeIIITPPS] redox potential values for these
iron(III) species are close to each other (14, 38, and 72 mV vs
NHE, for [FeIII(H2O)TPPS], Hb, and metMb, respec-
tively).27,31 Also, we observe a good correlation of the k1 and
the Fe(III), which is generally considered an electron-poor
species. However, in the models studied herein, the Fe(III)
species are high spin.47 Thus, there is one unpaired electron in
2
the dz orbital, which by the DFT calculation of the species
[FeIII(H2O)TPPS] is the HOMO orbital of the molecule. Also
DFT calculations for the complex trans-[RuII(NO+)(NH3)4(P-
(OEt)3)]3+ indicate that the LUMO and LUMO+1 orbitals,
both degenerate, are concentrated predominantly on the
nitrosonium ligand, thus suggesting a possible nucleophilic
attack of the Fe(III) on the nitrosonium ligand. The electron
transfer occurs after the formation of the intermediate, leading
to a second species, still with NO as bridging ligand, but with
the oxidized ruthenium and reduced iron centers. After the
electron is transferred, the bond between ruthenium and NO
begins to break, yielding [FeII(NO+)(TPPS)]3− and
[RuIII(H2O)]3+ as products, with the specific rate constants
(k2) as shown in Table 1.
k2 values with E0′Fe
values (Supporting Information, Figure
III/FeII
S5). Since the values of k1 and k2 for the same nitrosyl complex
do not differ significantly with the nature of the iron(III)
species, the steric hindrance of the iron(III) center does not
seem to be the main factor contributing to the values of the rate
constants.
The changes in the electronic spectra of the [FeIII(H2O)-
TPPS] by mixing solutions of trans-[RuII(NO+)(NH3)4(L)]3+
and [FeIII(H2O)TPPS] indicate that electron transfer occurs
between the ruthenium and iron centers. However, this
observation does not provide any information about the
association between these two ions in the absence of electron
transfer. This information was obtained by performing
experiments using differential pulse voltammetry and conduc-
tometry. The voltammograms for the reduction of the nitrosyl
ligand in the complexes trans-[RuII(NO+)(NH3)4(L)]3+ (L =
ImN, IsN, Nic, and P(OH)(OEt)2) were found to be
unchanged by the addition of [FeIII(H2O)TPPS] to the
The activation parameter values found indicate that the
reaction is exergonic. The values found for ΔH⧧ and ΔG⧧ are
coherent with other bimolecular reactions.46,48 Previously
studies49,50 involving the reaction between NO and
[FeIII(TPPS)] and metMb indicate that the water dissociation
is the first step for the reaction between iron(III) species and
NO. Ford and van Eldik described activation parameters for
these reactions: 70 3/71 2 kJ mol−1 and 100 4/82 7 J
mol−1 K−1 for ΔH⧧ and ΔS⧧ for [FeIII(TPPS)] and metMb,
respectively. These values are in reasonable agreement with the
values obtained in this work and would suggest that the NO
transfer, as an example of the other reported reactions with
iron(III) species described in the literature,49,50 is controlled by
the water dissociation step.
+
0
solution. Thus, no shift is observed in E(NO /NO ) and no
increase observed in the half-wave values (W1/2). This
information strongly suggests that for these complexes there
is no interaction at the nitrosyl ligand in the presence of the
iron compound. This is not the case for L = P(OEt)3 and
P(OMe)3 as previously mentioned. Conductometric measure-
ments provide additional support for this. Except for L =
P(OEt)3 and P(OMe)3, no changes were observed in the
solution conductance, for a 1 h period, when solutions of trans-
[RuII(NO+)(NH3)4(L)]3+ and [FeIII(H2O)TPPS] were mixed.
When L = P(OEt)3 and P(OMe)3, there is a substantial
conductance decrease within the first 10 min, after which the
conductance increases. This behavior is in agreement with that
expected, according to eqs 6 and 7.
It is interesting to observe that the value of ΔS⧧ is positive
for the formation of the binuclear species and negative for the
intermediate broken. This behavior is not expected, but can be
explained, in addition to the possible water dissociative
pathway, by the large solvation changes during the reactions,
mostly in the transition-state structures.44,45
Taking in account the reactants, the products, and the
postulated intermediate (optimized by DFT calculations) some
interesting points can be inferred. First, the value of ket between
the two metal centers tends to be slow, since there is an orbital
symmetry impediment for the electron transfer. The [RuII−
The absorbance versus time profile strongly suggests the
formation of a single intermediate species,44,45 supporting the
reactions represented in eq 6 and 7. In the second step, the
binuclear species dissociates, yielding the products in a
straightforward reaction. No evidence of rate saturation was
observed in plots of kobs versus CRu in the concentration range
studied. At iron concentrations higher than 1.0 × 10−4 mol L−1
and a 10-fold excess of ruthenium, a dark brown precipitate is
formed in a low yield (<5%). The characterization of this solid
using elemental analysis ICP-OS was inconclusive. However, an
EPR spectrum (Figure S6, Supporting Information) of this
solid at −263 °C showed the presence of two distinct iron
paramagnetic species. The g = 5.8 species is attributed to high-
spin Fe(III), probably [FeIII(H2O)TPPS], and the g = 2.03
species is described in the literature and attributed to
[FeII(NO●)TPPS] species.46
+
2
NO ] bond consists of a σ component involving the Ru dz
orbital and NO ligand and a π component involving the orbitals
Ru dzy and dzx and the NO pπ* orbitals. In the binuclear
species, the bond between Ru, Fe, and NO is formed by the
interaction of the pπ* orbital of [RuIINO+] fragment with the
2
dz orbital of Fe, which has σ symmetry. With this perspective,
the oxidation of the Ru(II) center will occur using the dzy or dzx
orbitals, which interact with both the NO+ and iron species. In
short, the electron transfer between the two metal centers will
occur through the ruthenium π-symmetry orbitals and iron σ
orbital. The symmetry difference makes the electron transfer a
slow process. DFT calculations show a delocalized bonding
orbital (HOMO−12) connecting the Ru, Fe, and NO+ centers,
with a ligand characteristic that could probably be the one
involved in the electron transfer. Figure S4 (Supporting
Information) shows the contour surface of HOMO−12 for
the binuclear species.
In the first step the formation of the binuclear species, with
the specific rate constants (k1) reported in Table 1, arises from
2
the interaction between the electron in the dz orbital of the
[FeIII(TPPS)]3− and the empty pπ* orbitals of the
[RuII(NO+)]3+ complex, passing through the first transition
state (TS#1). This suggests an electrophilic attack of an Fe(III)
species on the coordinated NO+ in the Ru(II) complex. At first
sight it seems unlikely that the nucleophile in this reaction is
After the electron transfer, the bond-breaking rate constant
between Ru(III) and NO+ is 2.4 × 10−3 s−1 for the reaction
between trans-[RuII(NO+)(NH3)4(P(OEt)3)]3+ and
[FeIII(TPPS)]3−, Table 1. There are few examples of water
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Inorganic Chemistry
Article
substitution in ruthenium(III) ammine complexes with a
phosphorus ligand in one of the axial positions, being limited
to the specific rate constant for substitution of isonicotinamide
by water in trans-[RuIII(IsN)(NH3)4(P(OEt)3)]3+, calculated as
5.0 × 10−5 s−1. Comparing the rate constants the specific rate
constant is found to be 48-fold higher for water substitution in
the binuclear complex. One possible explanation for the higher
specific rate constant for aquation of the binuclear complex is
the presence of Fe(II) bonded to the NO+, since the bond
between [FeII(NO+)] is stronger than [RuIII(NO+)], due to the
presence of back-bonding in the iron nitrosyl complex.
The electrochemical experiments and the DFT calculations
for the title reactions strongly suggest the formation of a
binuclear species, as described in eqs 6 and 7. Therefore, the
electroactive species at Ecp1 = −0.47 V was tentatively attributed
to the bridged nitrosonium ligand reduction, as described in eq
8. This is the site were the reduction would probably occur.
The NO reduction in the binuclear complex could be
coherently shifted to more negative potentials with respect to
that observed in the complex trans-[RuII(NO+)(NH3)4(P-
(OR)3)]3+ owing to the electron density delocalization along
the [Ru−(μNO)−Fe] bridge.
ASSOCIATED CONTENT
* Supporting Information
This material is available free of charge via the Internet at
http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
*E-mail: douglas@iqsc.usp.br.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors acknowledge FAPESP and CNPq (grant numbers
2012/2365-4 and 475631/2011-0, respectively) for the
financial support. The authors are also indebted to A.B.P.
Lever (York University), Bruce R. King (University of
Georgia), and Edward I. Solomon (Stanford University) for
helpful discussions during the preparation of the manuscript.
DEDICATION
Dedicated to the memory of Professor Edson Rodrigues.
■
The NO transfer reactions of manganese, iron, and
chromium complexes have already been reported in the
literature.13−19 However, the results described herein are the
first examples of this reaction with ruthenium nitrosyls.
The possibility of direct NO transfer to biological desired
targets demonstrated by the title complexes can be an
alternative pathway for NO delivery chemistry. Most of the
NO donors reported in the literature liberate NO, sponta-
neously or activated, in solution, and then the liberated NO
reacts with the biological targets. However, due to the reactivity
of NO, this species can react readily with other molecules,
decreasing the NO biological activity or leading to undesired
biological effects. The direct NO transfer discussed here may
circumvent these inconveniences since no NO is liberated in
the medium until the NO carrier hits the target, providing an
alternative pathway to form iron or thiol nitrosyl complexes in
biological systems. Also, not only myoglobin but also
hemoglobin reacts with the nitrosyl complexes, showing that
this reaction may be extended to other Fe(III)-containing
proteins.
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CONCLUSION
■
On the basis of the analysis of reaction products and kinetic
data the reactions of ruthenium nitrosyls and selected iron(III)
species were found to differ from other nitric oxide transfer
reactions previously reported. The nitrosonium ligand on the
ruthenium moiety acts as an electron transfer bridge between
the two metal centers, providing an unprecedented example of
an inner-sphere electron transfer process through an NO
bridge. The relatively stable intermediate species [Ru(μ-
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