Nitrosation of N-methylhydroxylamine by nitroprusside. A kinetic and mechanistic study

Article abstract of DOI:10.1039/b805329d

The kinetics of the reaction between aqueous solutions of Na ₂[Fe(CN)₅NO]?2H₂O (sodium pentacyanonitrosylferrate(ii), nitroprusside, SNP) and MeN(H)OH (N-methylhydroxylamine, MeHA) has been studied by means of UV-vis spectroscopy, using complementary solution techniques: FTIR/ATR, EPR, mass spectrometry and isotopic labeling (¹⁵NO), in the pH range 7.1-9.3, I = 1 M (NaCl). The main products were N-methyl-N-nitrosohydroxylamine (MeN(NO)OH) and [Fe(CN)₅H₂O]^3-, characterized as the [Fe(CN)₅(pyCONH₂)]^3- complex (pyCONH ₂ = isonicotinamide). No reaction occurred with Me₂NOH (N,N-dimethylhydroxylamine, Me₂HA) as nucleophile. The rate law was: R = k_exp [Fe(CN)₅NO^2-] × [MeN(H)OH] × [OH^-], with k_exp = 1.6 ± 0.2 × 10⁵ M^-2 s^-1, at 25.0 °C, and ΔH ^# = 34 ± 3 kJ mol^-1, ΔS^# = -32 ± 11 J K^-1 mol^-1, at pH 8.0. The proposed mechanism involves the formation of a precursor associative complex between SNP and MeHA, followed by an OH^--assisted reversible formation of a deprotonated adduct, [Fe(CN)₅(N(O)NMeOH)]^3-, and rapid dissociation of MeN(NO)OH. In excess SNP, the precursor complex reacts through a competitive one-electron-transfer path, forming the [Fe(CN)₅NO]^3- ion with slow production of small quantities of N₂O. The stoichiometry and mechanism of the main adduct-formation path are similar to those previously reported for hydroxylamine (HA) and related nucleophiles. The nitrosated product, MeN(NO)OH, decomposes thermally at physiological temperatures, slowly yielding NO. The Royal Society of Chemistry 2008.

Full text of DOI:10.1039/b805329d

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www.rsc.org/dalton | Dalton Transactions
Nitrosation of N-methylhydroxylamine by nitroprusside. A kinetic and
mechanistic study†
a
a
b
a
Mar ´ı a Marta Guti e´ rrez, Graciela Beatriz Alluisetti, Jos e´ Antonio Olabe and Valent ´ı n Tom a´ s Amorebieta*
Received 1st April 2008, Accepted 16th June 2008
First published as an Advance Article on the web 29th July 2008
DOI: 10.1039/b805329d
The kinetics of the reaction between aqueous solutions of Na
pentacyanonitrosylferrate(II), nitroprusside, SNP) and MeN(H)OH (N-methylhydroxylamine, MeHA)
2
[Fe(CN)
5
NO]·2H
2
O (sodium
has been studied by means of UV-vis spectroscopy, using complementary solution techniques:
1
5
FTIR/ATR, EPR, mass spectrometry and isotopic labeling ( NO), in the pH range 7.1–9.3, I = 1 M
NaCl). The main products were N-methyl-N-nitrosohydroxylamine (MeN(NO)OH) and
(
3
−
3−
[Fe(CN)
5
H
2
O] , characterized as the [Fe(CN)
5
(pyCONH
2
)] complex (pyCONH
2
= isonicotinamide).
No reaction occurred with Me
2
2
NOH (N,N-dimethylhydroxylamine, Me
2
HA) as nucleophile. The rate
−
−
5
−2 −1
law was: R = kexp [Fe(CN)
5
NO ] × [MeN(H)OH] × [OH ], with kexp = 1.6 ± 0.2 × 10 M s , at
◦
#
−1
#
−1
−1
2
5.0 C, and DH = 34 ± 3 kJ mol , DS = −32 ± 11 J K mol , at pH 8.0. The proposed mechanism
involves the formation of a precursor associative complex between SNP and MeHA, followed by an
−
3−
OH -assisted reversible formation of a deprotonated adduct, [Fe(CN)
5
(N(O)NMeOH)] , and rapid
dissociation of MeN(NO)OH. In excess SNP, the precursor complex reacts through a competitive
3
−
one-electron-transfer path, forming the [Fe(CN)
5
NO] ion with slow production of small quantities of
N
2
O. The stoichiometry and mechanism of the main adduct-formation path are similar to those
previously reported for hydroxylamine (HA) and related nucleophiles. The nitrosated product,
MeN(NO)OH, decomposes thermally at physiological temperatures, slowly yielding NO.
Introduction
deprotonations and/or redox transformations, with oxidation of
+
B and reduction of NO . Usually, the reactions comprise the
The reactivity of the nitrosyl group bound to transition metal
centers is a matter of increasing interest in the context of studies
on the chemistry and biochemistry of NO. Addition reactions
of nucleophiles (B) to nitrosonium (NO )-complexes have been
considered for a long time. Although a general stoichiometric
picture is well established, detailed kinetic and mechanistic
studies are scarce, mainly performed with sodium nitroprusside,
4,5
nitrosation of the B substrates. In addition to interest in the
1
,2
influence of the MX
the bound NO -groups, there is concern regarding the specific
properties of the nucleophiles in determining the stoichiometry
5
fragment on the electrophilic ability of
3
+
13
+
4
14
and mechanism of the addition reactions.
We report a kinetic and mechanistic study of the reactions of N-
methylhydroxylamine (MeHA) and N,N-dimethylhydroxylamine
5
Na
2
[Fe(CN)
5
NO]·2H
2
O (SNP). The latter emphasis may be
(
Me
2
HA) with SNP. This is complementary to the previous work
6
understood in terms of the well known hypotensive ability of SNP.
10
with HA. Recently, a diverse stoichiometric and mechanistic sce-
−
7
Some biorelevant nucleophiles are OH , nitrogenated species,
nario was found for the nucleophilic additions of hydrazine (N
2
4
H )
8
9
10
viz., NH , amines and amino acids, hydroxylamine (HA),
3
and substituted derivatives: Me-hydrazine, 1,1-(Me)
2
hydrazine
11
−
12
nitrite, and thiolates, RS (cysteine, glutathione, etc). The
14
and 1,2-(Me)
2
hydrazine, toward SNP. In contrast to the general
underlying mechanisms comprise an initial reversible addition of B
common path leading to N
2
O as a main reduction product
hydrazine reactant led to the full six-
+
+
x
to the NO containing complex, of general formula [MX
5
(NO )]
+
of NO , the 1,2-(Me)
2
II
(
M
= Fe, Ru, Os; X = amines, polypyridines, porphyrins,
+
electron reduction of NO to NH , associated with the additional
3
x
etc.). The adducts, {[MX
5
(N(O)B} , may be subsequently reactive
formation of a very stable product, azomethane (MeN=NMe).
Such profound changes in the reactivity might have a significant
biochemical relevance for HA-derivatives. HA is endogenously
synthesized in the body and has a metabolic role in diverse
through some type of reorganization, most commonly involving
a
Department of Chemistry, Facultad de Ciencias Exactas y Naturales,
Universidad Nacional de Mar del Plata, Funes y Roca, Mar del Plata,
B7602AYL, Argentina. E-mail: amorebie@mdp.edu.ar
3
processes. Although the three compounds: HA, MeHA and
b
Department of Inorganic, Analytical and Physical Chemistry and
Me
2
HA form nitroxide radicals, only HA is able to generate free
INQUIMAE, CONICET, Facultad de Ciencias Exactas y Naturales,
Universidad de Buenos Aires, Pabell o´ n 2, Ciudad Universitaria, C1428EHA,
Buenos Aires, Argentina
15
NO, and it has been reported that the vasorelaxing activity of HA
decreases with alkylation. The reactions of HA and derivatives
generating nitrosyl-compounds, or reacting with them with
16
17
†
Electronic supplementary information (ESI) available: ESR spectrum in
2−
aqueous solution of the [Fe(CN)
4
NO] radical (Fig. 1) formed through
formation of molecules with intermediate redox states (N , NO,
2
3−
5
cyanide labilization of the [Fe(CN) NO] intermediate, and Eyring plot
N
2
O) are an example of the rich chemistry associated with the
for the calculation of activation parameters, including a Table with
experimental rate constants at different temperatures, pH 8.0 (Fig. 2).
See DOI: 10.1039/b805329d
natural nitrogen-redox cycles, including bacterial transformations
18
in soils (nitrification and denitrification).
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Experimental
some NaCl, was filtered off and washed several times with small
portions of cold diethyl ether.
N-Methylhydroxylamine hydrochloride, MeN(H)OH·HCl (>98%)
and N,N-dimethylhydroxylamine hydrochloride, (Me)
2
NOH·
O was from
) was from Aldrich.
All were analytical or reagent grade, and were used without
Results
HCl (>98%) were from Fluka, Na
Merck, and isonicotinamide (pyCONH
2
[Fe(CN)
5
NO]·2H
2
2
Fig. 1 shows the monoexponential increase in the absorbance
of the final product, [Fe(CN) (pyCONH )] , either in excess
conditions of MeHA or of SNP, at 25.0 C. No reaction at
all was observed by using Me HA as the reactant. With excess
3
−
5
2
1
5
◦
further purification. Na
2
[Fe(CN)
5
NO]·2H
2
O was prepared as
(99 atom% N) from
19
15
15
previously described, by using Na NO
2
2
MSD Isotopes. N-Methyl-N-nitrosohydroxylamine as the sodium
MeHA (Fig. 1a), a nearly full conversion (95%) of initial SNP
3
−
salt (Na[MeN(NO)O]) was synthesized according to literature
to [Fe(CN) (pyCONH )] was obtained, with no evolution of
5
2
20
procedures, see below. Buffer solutions based on phosphates or
gaseous products. The degree of advancement of the reaction was
also monitored by FTIR-ATR. Fig. 2 (top) shows the disappear-
borax and NaCl were prepared in the range 7.1 ± 0.2 < pH <
−
1
9
.3 ± 0.2, by using de-ionized water. Ionic strength was adjusted
ance of the initial stretching modes of cyanide (m , 2142 cm ),
CN
−
1
26
−1
to 1 M with NaCl. A calibrated pH-meter (Hanna HI 9231) was
employed, using Merck standard buffers.
and nitrosyl (mNO, 1935 cm ) in SNP. The new band at 2042 cm
(mCN) reflects the formation of [Fe(CN) (pyCONH )] . In Fig. 2
(bottom), other bands at 953, 1057, 1217, 1278 and 1370 cm can
be appreciated, corresponding to the diazeniumdiolate functional
group [–N(NO)O] , a structure that is present in N-methyl-N-
3
− 27
5
2
−
1
UV-vis spectra and kinetics were measured on an Ocean Optics
HR 2000, CG-UV-NIR diode array spectrophotometer, using
quartz cuvettes. Some kinetic studies were carried out with a Hi-
Tech Scientific SFA-20 stopped-flow accessory. The EPR spectra
were measured with a Bruker ER 200D X-band spectrometer,
previously calibrated with the reference spectrum of 2,2,6,6-
−
28,29
nitrosohydroxylamine, MeN(NO)OH.
etry may be described by eqn (1) and (2):
The overall stoichiom-
2
−
−
3−
[
Fe(CN)
5
NO] + MeN(H)OH + OH → [Fe(CN)
5
2
H O]
tetramethylpiperidine-1-oxyl (TEMPO, a
N
(NO) = 1.72 mT, g =
+
MeN(NO)OH
(1)
(2)
21
2.0051) in water (1–5 lM). FTIR/ATR spectra were recorded
with a Perkin Elmer Spectrum BX spectrophotometer, equipped
with a standard pre-mounted horizontal ATR accessory with a flat
sampling plate of ZnSe. Argon saturated buffered solutions of the
reactants; contained in 10 ml glass-syringes were mixed in a 500 ll
homemade flow-cell mounted on the ZnSe crystal. The samples
were transferred into the cell by aspiration with a syringe. The
spectra were obtained in buffered solutions as differences from
the SNP or MeHA solutions plus isonicotinamide as the used
scavenger. An Extrel Emba II quadrupolar mass spectrometer was
3
−
3−
[
Fe(CN)
5
H
2
O] + pyCONH
2
→ [Fe(CN)
5
(pyCONH )]
2
+
H
2
O
14,22
used for identifying gaseous products, as described elsewhere.
The kinetic studies on the reaction between SNP and MeHA
◦
were mainly performed at 25.0 ± 0.2 C, on buffered, argon satu-
rated solutions, under pseudo-order conditions in SNP or MeHA,
at different pHs. In excess MeHA conditions, the temperature
◦
range was extended to 12–40 C for obtaining activation parame-
ters. A huge excess of isonicotinamide was used as a scavenger for
3
−
−1
−1 23
the [Fe(CN)
5
H
2
O] product (kmax 440 nm, e = 640 M cm ),
(pyCONH )]
3
−
forming the stable and intensely colored [Fe(CN)
5
2
−
1
−1 24
complex (kmax 435 nm, e = 4570 M cm ). This trapping
procedure was useful for sensitivity purposes, and also allowed the
3
−
Fig. 1 Absorbance of [Fe(CN) (pyCONH )]3−, measured at 440 nm, vs
exclusion of the main product [Fe(CN)
5
H
2
O] from the reaction
5
2
25
medium, precluding its further reactivity with MeHA. In a
typical run, freshly prepared buffered solutions of 0.1–50 mM
SNP were diluted in the spectrophotometer cell (1 or 0.1 cm path)
containing an aliquot of 0.1–70 mM MeHA and 50–250 mM
isonicotinamide, with final I = 1 M (NaCl).
time for the reaction of SNP with MeHA in the presence of 140 mM
◦
pyCONH
2
, pH 8.7, I = 1M (NaCl), T = 25.0 C. (a) SNP 0.14 mM,
MeHA 3.1 mM; (b) SNP 3.5 mM, MeHA 0.154 mM.
Reaction (2) has been independently measured by stopped-
−
1
−1
◦
30
For the synthesis of Na[MeN(NO)O], one gram of
MeN(H)OH.HCl was dissolved in a minimum amount of ethanol
flow techniques, with k
2
= 296 M
s
at 25.0 C. Under
the selected working conditions (Table 1), reaction (2) evolves
several orders of magnitude faster than (1). The MeN(NO)OH
product was additionally characterized in the clarified reaction
solutions by UV-vis spectroscopy, after room-temperature vacuum
3
in a 0.025 dm round-bottom flask, equipped with a mechanical
stirrer. The solution was neutralized with the theoretical amount
◦
of solid NaOH (0.48 g), and cooled below 0 C in an ice–salt bath.
2
8,29
Cooled N-butylnitrite (theoretical amount, 2.4 mL) was added
distillation of the exhausted reaction mixtures.
The spec-
very slowly through a funnel, maintaining the temperature of the
reaction mixture below 10 C. After stirring for 10 minutes, the
mixture was concentrated under vacuum. The product, containing
tra and other properties of this compound were identical to
those from synthetic Na[MeN(NO)O] (see Experimental section).
The protonated structure MeN(NO)OH absorbs at ca. 230 nm
◦
5
026 | Dalton Trans., 2008, 5025–5030
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In addition to the markers for SNP consumption and for the
3
−
formation of [Fe(CN)
5
(pyCONH
2
)] , Fig. 3 shows a new cyanide
absorption at 2086 cm . Fig. 1 ESI † shows an EPR spectrum
containing a 1 : 1 : 1 triplet characterized by a
(NO) = 1.47 mT and
g = 2.0293. Both IR and EPR new features support the formation
of the [Fe(CN) NO] radical.
−
1
N
3
−
26,31
5
Fig. 2 HATR (horizontal attenuated total reflectance) spectra for the
addition reaction, with 200 mM MeHA and 14 mM SNP, in the
presence of 200 mM pyCONH
2
, pH 9.3, I = 1M (NaCl), room
temperature. Top: (A) Spectrum of the reactant, SNP. (B) mCN for the
3−
[
Fe(CN)
5 2
(pyCONH )] product. Bottom: (A) Spectrum of independently
synthesized Na[CH
frequencies of the [–N(NO)O ] group are indicated. (B) Spectrum of the
reaction product.
3
N(NO)O] in aqueous solution. The characteristic
−
Fig. 3 HATR spectra for the addition reaction, with 600 mM SNP, 23 mM
MeHA, 200 mM pyCONH
2
, pH 9.3, I = 1 M (NaCl), room temperature.
Table 1 Rate constants for the reaction of SNP with MeHA at different
(
A) Initial spectrum of SNP. (B and C) Spectra during reaction progress.
a,b
concentrations of reactants and pH
3
−1
−5
−2 −1
As seen in Fig. 1a, the individual kinetic runs for the buildup
SNP/mM
MeHA/mM
pH
10 kobs/s
10
kexp/M
s
3
−
of [Fe(CN)
5
(pyCONH )] gave good single exponential behavior
2
2
8
3
2.0
9.0
1.9
3.7
6.0
11.0
16.4
25
35.3
54.5
3.6
7.1
7.1
7.1
7.1
7.1
7.1
7.5
7.5
8.2
8.2
8.7
8.7
8.8
8.8
8.8
9.3
9.3
9.3
2.30
0.74
0.10
0.22
0.37
0.50
1.98
2.83
0.82
1.53
3.20
2.30
1.32
2.80
6.71
10.0
10.3
21.9
2.0
1.5
1.4
1.6
1.8
1.6
1.8
1.6
1.4
1.4
1.8
1.5
1.5
1.6
1.6
1.6
1.6
1.7
(r ≥ 0.999), yielding the pseudo-first order rate constants, k
obs
(
Table 1), which display a first-order dependence on the analytical
3
0
1
0
2
2
0
0
3
3
0
0
0
0
0
0
.2
.63
.2
.23
.2
.2
.18
.19
.5
−
concentrations of MeHA and OH .
Activation parameters obtained through an Eyring plot lead to
#
−1
#
−1
−1
DH = 34 ± 3 kJ mol and DS = −32 ± 11 J K mol , at pH 8.0
Fig. 2 ESI†). Given the specific stoichiometric features appearing
when SNP is in excess over MeHA (Fig. 1b), we used the initial
(
32
7.0
rate method for the kinetic analysis of the exponential increase.
0.07
0.14
1.4
2.8
6.9
3.1
3.2
6.5
The resulting rates were proportional to the initial concentration
.1
of MeHA, yielding kobs values (Table 1), which also correlated
.13
.13
.25
.36
.08
.08
−
linearly with the concentrations of SNP and OH .
Fig. 4 summarizes the overall kinetic results through a logarith-
mic plot. We conclude that the same third-order rate law holds
for the nucleophilic addition process, either in excess conditions
of MeHA or SNP, eqn (3):
a
◦
−
Monitored at 440 nm, 25 C, I = 1 M (NaCl). The concentration of OH
−
14
b
was computed from the pH, with K
averaged for each entry.
w
= 1.0 × 10
.
Triplicate runs were
2−
−
R = k
3
× [Fe(CN)
5
NO ] × [MeN(H)OH] × [OH ]
(3)
5
−2 −1
A linear fit of the data yields k
3
= kexp = (1.6 ± 0.2) × 10 M
s
◦
(
T = 25.0 C). The unreactivity of the MeN(NO)OH product
−
1
−1
−
2−
3−
(
e ≈ 7000 M cm ), and the [MeN(NO)O] form shifts to ca.
toward [Fe(CN)
5
NO] or [Fe(CN)
5
H O] was monitored by
2
−
1
−1
2
50 nm (e ≈ 8000 M cm ).
performing independent experiments. No radical formation could
be detected in these assays.
The stoichiometric and kinetic picture is shown to be signifi-
1
5
cantly different when using excess SNP over MeHA. A yield of
A final, independent experiment, showed the formation of NO
3
−
15
only ca. 75% of [Fe(CN)
time scale (Fig. 1b). More [Fe(CN)
through a very slow process, which also reveals the formation
of N O.
5
(pyCONH
2
)] is achieved in the minutes
(m/z 31) and
N O (m/z 46) when the exhausted solutions were
2
◦
3
−
(pyCONH
2
)] is formed
warmed at 35–40 C.
5
2
Discussion
Additional, direct evidence for the presence of a possible
competitive path to the main process described by eqn (1) and
2) comes from FTIR and EPR measurements.
5
−2 −1
The value of kexp = (1.6 ± 0.2) × 10 M
s
for the nucleophilic
(
addition reaction is only slightly smaller than that found in
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3
−
decomposition, leading to [Fe(CN)
5
(H O)] as the final product.
2
Exceptionally, an intermediate could be detected in the reaction of
azide with SNP, under similar conditions to those in the present
−
1
study, showing a decomposition rate of 0.2 s , independent of
10,34
azide concentration.
It is highly feasible that other N-binding
adducts may reorganize and dissociate with rates of the same
order of magnitude, given that similar Fe–N bonds must be
broken.
5
As reviewed recently, a generalized approach to nucleophilic
reactivity gives a strong support to mechanistic pathways involving
a comparatively slow formation of the adduct-intermediates.
Further evidence in favour of the sequence (4)–(6) with a slow k
5
step is given by the requirement that a removable H-atom must be
placed at the adjacent position of the nucleophilic N-atom of HA
or MeHA. For this reason, Me
2
HA was shown to be unreactive, as
8
−
1
was the case with NMe . The modest decrease of k for MeHA
3
exp
Fig. 4 Logarithmic plot of the pseudo-first-order rate constants (kobs, s
)
−
2
vs ([X] × [OH ]/M ) with [X] = MeHA or SNP, at I = 1 M (NaCl),
vs HA is of the same order of magnitude as found for hydrazine
◦
14
2
5.0 C. Excess of MeHA: ꢀ, pH 9.3; ᭺, pH 8.8; ꢀ, pH 8.2; ꢁ, pH 7.5; ♦,
and its methylsubstituted derivative, probably related to steric
pH 7.1. Excess of SNP: ✩, pH 8.7 and 7.1.
effects of the Me group influencing either the slower formation
of the adduct or its faster back dissociation (eqn (5)). Finally,
the negative values of the activation entropies found by us and
5
−2
−1
the reaction of SNP with HA, kexp = 4.5 × 10
M
s , at
5,7,10,12
◦
10
others
are also consistent with an associative mechanism for
behaving as rate-
2
5.0 ± 0.2 C. We propose a three-step mechanism involving
the nucleophilic additions, as well as with k
controlling.
5
an associative pre-equilibrium between the two main reactants
35
−
(
eqn (4)), followed by an OH -assisted process forming an addition
intermediate (eqn (5)), in which the N-atom of MeHA forms
a covalent bond with the N-atom of the NO ligand in SNP.
Reaction (6) describes the dissociation of the adduct through the
cleavage of the Fe–N bond, releasing a nitrosation product, N-
methyl-N-nitrosohydroxylamine.
The formation of NO at physiological temperatures may be
traced to reaction (7), namely a secondary process involving bi-
molecular decomposition of N-methyl-N-nitrosohydroxylamine,
+
28
also producing azoxymethane. In this way, MeHA might behave
36
as a slow NO-donor, in contrast with HA, which rapidly
generates N O.
2
2
−
[
Fe(CN)
5
NO] + MeN(H)OH ꢀ
2
−
15
15
=
N(O)Me + H O + 2 NO
(7)
{[Fe(CN)
5
NO] ·[MeN(H)OH]}
(4)
(5)
(6)
2 MeN( NO)OH → MeN
2
Finally, the complex stoichiometry described above in excess
SNP conditions (Fig. 1b) must be accounted for. By considering
the previously analyzed mechanistic framework, we propose
that the precursor complex (eqn (4)) is competitively reactive
with respect to the adduct-intermediate production (eqn (5)),
through a new electron-transfer channel. The indirect (decreased
initial SNP consumption) and direct experimental evidence (IR,
2
−
−
{
[Fe(CN)
5
NO] ·[MeN(H)OH]} + OH ꢀ
(N(O)NMeOH)] + H
3
−
[Fe(CN)
5
2
O
3
−
3−
[
Fe(CN)
5
(N(O)NMeOH)] + H
2
O → [Fe(CN)
5
(H O)]
2
+
MeN(NO)OH
A
steady-state mechanistic treatment for the adduct-
intermediate leads to a rate law which is consistent with the
experimentally found one. Following the fast prior equilibrium
EPR) allow us to propose reaction (8), accordingly with the
3−
formation of [Fe(CN)
of MeHA.
5
NO] and undetermined oxidized products
−
1
13
(
eqn (4), with K
be equalized to kexp = K
may be considered: (a) If k−5 >> k
and the rate law would represent a process controlled by the slow
adduct decomposition reaction (6). (b) If k−5 << k
. As discussed below, the latter situation is more plausible,
4
= ca. 0.5 M ), the value of kexp in eqn (3) can
× k × k /(k−5 + k ). Two limiting cases
, then kexp = K × K × k
37,38
4
5
6
6
2
−
3−
{
[Fe(CN)
5
NO] ·[MeN(H)OH]} → [Fe(CN)
5
NO]
6
4
5
6
,
+
(MeHA)ox
(8)
6
, then kexp
=
Alternative paths for SNP reductions, involving either direct
3
−
K
4
× k
5
one-electron transfer leading to [Fe(CN) NO] or nucleophilic
5
and means that the intermediate formation step is rate-controlling.
A significant reorganization energy has been calculated for the
conversion of linear Fe–NO to bent Fe–N(O)B structures for
additions (formal two-electron transfer) have also been de-
scribed for the reactions of thiolates with SNP, without clear
+
39
kinetic discrimination. Finally, the very slow conversion of
−
13,14,33
3−
3−
adducts with B = OH and nitrogen hydrides.
Different
[Fe(CN)
5
NO] into [Fe(CN)
5
(pyCONH )] may be traced to
2
3
−
mechanistic interpretations have been given in the literature to the
the small dissociation rates of NO from [Fe(CN)
5
NO] or
7–10,12–14
2−
values of the experimental rate constants.
For nucleophiles
[Fe(CN)
4
NO] (the latter is formed through cyanide labilization
−
−
−5 −1
◦
40
forming fairly stable and detectable adducts (B = OH , SR ), the
at pHs < 9), with k−NO = ca. 10
s at 25 C. It has been shown
reactions have been studied by monitoring the absorbance increase
that the release of NO leads to an intermediate dinitrosyl species,
7,12,13
2−
of the deprotonated intermediates.
Thus, the mechanism
proposed to be [Fe(CN)
into SNP and N
of the reactions occurring subsequently to eqn (8), this is a
4
(NO)
2
] , which further disproportionates
O. We believe that in the hours-time scale
can be described by reactions like (4) and (5), with (6) being
irrelevant under these conditions. In contrast, the adducts become
undetectable for most of the nitrogen hydrides, suggesting a fast
2
40
feasible path for N
2
O formation. The evidence comes from the
5
028 | Dalton Trans., 2008, 5025–5030
This journal is © The Royal Society of Chemistry 2008

View Article Online
1
5
14
unique
N
2
O product, free of mixed species with N. Thus, all
7 J. H. Swinehart and P. A. Rock, Inorg. Chem., 1966, 5, 573; J. Masek
and H. Wendt, Inorg. Chim. Acta, 1969, 3, 455.
1
5
the N O comes from N originally present in labeled SNP. We
must discard a reduction event at the nitrosohydroxylamine
moiety.
2
8
N. E. Katz, M. A. Blesa, J. A. Olabe and P. J. Aymonino, J. Inorg. Nucl.
Chem., 1980, 42, 581; I. Maciejowska, Z. Stasicka, G. Stochel and R.
van Eldik, J. Chem. Soc., Dalton Trans., 1999, 3643.
L. Dozsa, V. Kormos and M. T. Beck, Inorg. Chim. Acta, 1984, 82, 69;
A. Katho, Z. Bodi, L. Dozsa and M. T. Beck, Inorg. Chim. Acta, 1984,
83, 145.
9
Conclusions
1
1
0 S. K. Wolfe, C. Andrade and J. H. Swinehart, Inorg. Chem., 1974, 13,
The reaction of MeHA with SNP evolves as described in
Scheme 1. An initial association of reactants is followed by a
predominant path with reversible adduct-formation, implying a
covalent attachment of the nucleophilic N-atom of MeHA to the
N-atom of the nitrosonium ligand in SNP, with OH -assisted
deprotonation. Further fast cleavage of the Fe–N bond gives
2567.
1 B. O. Fernandez and P. C. Ford, J. Am. Chem. Soc., 2003, 125,
1
0510.
1
1
2 M. D. Johnson and R. G. Wilkins, Inorg. Chem., 1984, 23, 231.
3 F. Roncaroli, M. E. Ruggiero, D. W. Franco, G. L. Estiu and J. A.
Olabe, Inorg. Chem., 2002, 41, 5760.
−
1
1
1
4 M. M. Guti e´ rrez, V. T. Amorebieta, G. L. Estiu and J. A. Olabe, J. Am.
Chem. Soc., 2002, 124, 10307.
5 J. Taira, V. Misil and P. Riesz, Biochim. Biophys. Acta, 1997, 1336,
502.
6 G. Thomas and P. W. Ramwell, Biochem. Biophys. Res. Commun., 1989,
164, 889.
3
−
[
Fe(CN)
5
H O] and a soluble nitrosation product, N-methyl-
2
N-nitrosohydroxylamine (MeN(NO)OH). With excess SNP, a
competitive electron-transfer path is available for the initial asso-
3
−
ciation complex, leading to [Fe(CN)
decomposes very slowly forming N
rate laws in the concentrations of complex, nucleophile and OH
are the same for the reactions of SNP with HA and MeHA, with
closely similar rate constants, facile deprotonation processes allow
5
NO] , which subsequently
O. Although the third-order
1
1
7 K. Wieghardt, Adv. Inorg. Bioinorg. Mech., 1984, 3, 213.
8 I. M. Wasser, S. de Vries, P. Mo e¨ nne-Loccoz, I. Schr o¨ der and K. D.
Karlin, Chem. Rev., 2002, 102, 1201.
2
−
1
2
9 M. E Chac o´ n Villalba, E. L. Varetti and P. J. Aymonino, Vib. Spectrosc.,
1
997, 14, 275.
0 C. S. Marvel and O. Kamm, J. Am. Chem. Soc., 1919, 41, 276.
the formation and rapid release of N
2
O in the case of HA. In
21 K. Stolze and H. Nohl, Free Radical Res. Commun., 1990, 8, 123;
M. A. M. No e¨ l, R. E. Allendoerfer and R. A. Osteryoung, J. Phys.
Chem., 1992, 96, 2391; J. J. Testa, M. A. Grela and M. I. Litter, Environ.
Sci. Technol., 2004, 38, 1589.
2 G. B. Alluisetti, A. E. Almaraz, V. T. Amorebieta, F. Doctorovich and
J. A. Olabe, J. Am. Chem. Soc., 2004, 126, 13432.
3 H. E. Toma, Inorg. Chim. Acta, 1975, 15, 205.
4 H. E. Toma and J. M. Malin, Inorg. Chem., 1973, 12, 1039.
5 M. M. Guti e´ rrez, G. B. Alluisetti and V. T. Amorebieta, unpublished
work.
contrast, the presence of the Me group favors the dissociation of
MeN(NO)OH. This is a toxic chemical, behaving as a slow NO-
donor, and could react similarly to the N-nitrosamines, which are
well-known chemical carcinogens that are metabolized to strongly
alkylating electrophiles reacting with DNA at several nucleophilic
2
2
2
2
41
sites.
2
2
2
6 J. D. Schwane and M. T. Ashby, J. Am. Chem. Soc., 2002, 124,
6
822.
7 P. J. Morando, V. I. E. Bruy e` re, M. A. Blesa and J. A. Olabe, Transition
Met. Chem., 1983, 8, 999.
8 L. K. Keefer, J. L. Flippen-Anderson, C. George, A. P. Shanklin, M.
Tambra, D. C. Dunams, J. E. Saavedra, E. S. Sagan and D. S. Bohle,
Nitric Oxide, 2001, 5, 377.
2
3
3
9 J. A. Hrabie and L. K. Keefer, Chem. Rev., 2002, 102, 1135.
0 H. E. Toma and J. M. Malin, Inorg. Chem., 1973, 12, 2080.
1 K. Szacilowski, J. Oszajca, A. Barbieri, A. Karocki, Z. Sojka, S. Sostero,
R. Boaretto and Z. Stasicka, J. Photochem. Photobiol., A, 2001, 143,
9
9, and references therein; L. Grossi and S. D’Angelo, J. Med. Chem.,
Scheme 1
2005, 48, 2622 and references therein.
3
2 R. G. Wilkins, Kinetics and Mechanisms of Reactions of Transi-
tion Metal Complexes, VCH Verlag, Weinheim, Germany, 2nd edn,
1
991.
3
3
3 J. A. Olabe and G. L. Esti u´ , Inorg. Chem., 2003, 42, 4873.
Acknowledgements
4 An intermediate J, absorbing at 445 nm, has been claimed for the
1
0
reaction of HA with SNP. In fact, this species should be best assigned
2
3
This work has been supported by the University of Mar del Plata,
ANPCYT and CONICET. V.T.A. and J.A.O are members of the
scientific staff of CONICET.
3−
to [Fe(CN)
5
H
2
O]
,
and we believe that the authors have really
measured the rate of formation of the final product, as we presently
do. This is supported by the identical rate-law and similar values for
kexp and activation parameters for HA and MeHA.
3
5 The values calculated by us through an Eyring plot of the data for
1
0
#
−1
#
the addition of HA are: DH = 40 ± 3 kJ mol and DS = −13 ±
Notes and references
−
1
−1
2
J K mol , in expected close agreement with the presently reported
1
2
P. C. Ford and I. M. Lorkovic, Chem. Rev., 2002, 102, 993.
ones for MeHA. As the measured values reflect composite quantities
(reactions (4) and (5)), we estimated the activation parameters for
F. Roncaroli, M. Videla, L. D. Slep and J. A. Olabe, Coord. Chem. Rev.,
−
1
−1
−1
#
#
2
007, 251, 1903.
reaction (4) as ca. 1.5 kJ mol and 8 J K mol for DH and DS ,
13
3
J. L. E. Ignarro, Nitric Oxide, Biology and Photobiology, Academic
Press, San Diego, CA, 2000; Methods in Nitric Oxide Research, ed.
M. Feelisch and J. S. Stamler, Wiley, New York, 1996; G. B. Richter-
Addo and P. Legdzins, Metal Nitrosyls, Oxford University Press, New
York, 1992; J. A. McCleverty, Chem. Rev., 2004, 104, 403.
F. Bottomley, in Reactions of Coordinated Ligands, ed. P. S. Braterman,
Plenum Publishing Corp., New York, 1989, vol. 2.
respectively, revealing a minor contribution.
36 P. G. Wang, M. Xian, X. Tang, X. Wu, Z. Wen, T. Cai and A. J. Janczuk,
Chem. Rev., 2002, 102, 1091.
37 A question remains on the accessibility of the electron-transfer path
in excess of MeHA. The reproducible 95% yield of SNP conversion
(predominance of the addition path) suggests that a minor contribution
of the electron-transfer path might be operative, although no direct
EPR evidence has been obtained. Anyway, we may propose a reasonable
explanation for the significant contribution of the electron-transfer
4
5
6
J. A. Olabe, Adv. Inorg. Chem., 2004, 55, 61.
A. R. Butler and I. L. Megson, Chem. Rev., 2002, 102, 1155.
This journal is © The Royal Society of Chemistry 2008
Dalton Trans., 2008, 5025–5030 | 5029

View Article Online
+
path under excess SNP conditions, given that NO maintains its
39 P. Morando, E. B. Borghi, L. M. Schteingart and M. A. Blesa, J. Chem.
Soc., Dalton Trans., 1981, 435; K. Szacilowski, A. Wanat, A. Barbieri,
E. Wasiliewska, M. Witko, G. Stochel and Z. Stasicka, New J. Chem.,
2002, 26, 1495.
oxidizing ability in the precursor complex. On the other hand, with an
excess of MeHA, the adduct-formation path becomes much favored
because of the H-bonding stabilization of the adduct, associated
with the specific interactions between MeHA and the donor cyano-
40 F. Roncaroli, R. Van Eldik and J. A. Olabe, Inorg. Chem., 2005, 44,
3
8
ligands .
2781.
3
8 D. A. Estrin, L. M. Baraldo, L. D. Slep, B. C. Barja, J. A. Olabe, L.
Paglieri and G. Corongiu, Inorg. Chem., 1996, 35, 3897.
41 S. R. Tannenbaum, S. Tamir, T. de Rojas-Walker and J. S. Wishnok,
ACS Symp. Ser., 1994, 553, 120.
5
030 | Dalton Trans., 2008, 5025–5030
This journal is © The Royal Society of Chemistry 2008