Stability of phosphite coordinated to ruthenium(II) in aqueous media

Article abstract of DOI:10.1016/j.poly.2014.06.002

Changes in the reactivity of phosphorus(III) esters, which are promoted by coordination to the ruthenium(II) metal centre, were the focus of this study. Nuclear magnetic resonance data, which were acquired as a function of time, suggest that the phosphite coordination to the ruthenium(II) centre stabilises these molecules in terms of hydrolysis. This stabilisation is greater when the coordination occurs to the trans-[Ru(H₂O)(NH₃) ₄]²⁺ rather than to the trans-[Ru(NO)(NH₃) ₄]³⁺ fragment, and these results are interpreted considering the 4dπ(Ru^II) → 3dπ(P(III)) back-bonding interactions. The correlation between the data on alkyl phosphite hydrolysis constants in trans-[Ru(NO)(NH₃)₄P(III)]^{n +} (P(III) = P(OEt)₃, P(O)(OEt)₂, P(O ⁱPr)₃ and P(OBu)₃) complexes and the δ_13C data show that the hydrolysis of phosphites that are coordinated to Ru(II) preferably occurs via the Michaelis-Arbuzov mechanism. Only the nitrosyl complex, where P(III) = P(OMe)₃, did not exhibit this correlation, which suggests that the hydrolysis likely occurs via the Aksnes mechanism in this case.

Full text of DOI:10.1016/j.poly.2014.06.002

Polyhedron 81 (2014) 238–244
Contents lists available at ScienceDirect
Polyhedron
journal homepage: www.elsevier.com/locate/poly
Stability of phosphite coordinated to ruthenium(II) in aqueous media
⇑
Daniela R. Truzzi, Douglas W. Franco
Departamento de Química e Física Molecular, Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São-carlense, 400, Centro, São Carlos, São Paulo, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
Changes in the reactivity of phosphorus(III) esters, which are promoted by coordination to the ruthe-
nium(II) metal centre, were the focus of this study. Nuclear magnetic resonance data, which were
acquired as a function of time, suggest that the phosphite coordination to the ruthenium(II) centre
stabilises these molecules in terms of hydrolysis. This stabilisation is greater when the coordination
occurs to the trans-[Ru(H2O)(NH3)4]2+ rather than to the trans-[Ru(NO)(NH3)4]3+ fragment, and these
Received 10 April 2014
Accepted 3 June 2014
Available online 13 June 2014
results are interpreted considering the 4dp p(P(III)) back-bonding interactions. The correlation
(RuII) ? 3d
Keywords:
Phosphorus
Ruthenium
NO-donors
Reactivity
Phosphite
between the data on alkyl phosphite hydrolysis constants in trans-[Ru(NO)(NH3)4P(III)]n+ (P(III) = P(OEt)3,
P(O)(OEt)2, P(OiPr)3 and P(OBu)3) complexes and the d13C data show that the hydrolysis of phosphites that
are coordinated to Ru(II) preferably occurs via the Michaelis–Arbuzov mechanism. Only the nitrosyl
complex, where P(III) = P(OMe)3, did not exhibit this correlation, which suggests that the hydrolysis likely
occurs via the Aksnes mechanism in this case.
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
breaks the O–C bond (Fig. 1a). However, based on the analysis of
the phosphite hydrolysis product and data obtained using infrared
The uses of phosphorus(III) to tailor metal complexes for catal-
ysis and biochemistry applications have been extensively studied
[1,2], and the emphasis was generally on the induced changes on
the properties of the metal centre. However, few data discuss the
ability of the metal centre to induce changes in the reactivity of
the phosphorus(III) ligands.
spectroscopy and labelled water, Aksnes [9,10] suggested that the
phosphite hydrolysis preferentially occurs via a nucleophilic attack
on the phosphorus atom and the consequential breakage of the
P–O bond (Fig. 1b).
The hydrolysis of phosphites and phosphates is also notably
sensitive to acid catalysis [11]. Studies involving the retention of
an alcohol configuration [12] have shown that acid hydrolysis in
phosphanes occurs through both O–C [8] and P–O [9,10]
bond-break mechanisms.
Phosphites (P(OR)3) are phosphorus(III) compounds that coordi-
nates to metal centre through both a
electron pair of the phosphorus to empty orbital of the metal,
and a -backdonation from filled d-orbital of the metal to orbitals
of appropriated energy and -symmetry on phosphite ligand [3,4].
This -acid character of the phosphites can be tuned according to
r-donation of the lone
p
Metal complexes with coordinated phosphite, such as
p
trans-[Ru(H2O)(NH3)4P(OR)3](PF6)2,
where
P(OR)3 = P(OMe)3,
p
P(OEt)3, P(OiPr)3 and P(OBu)3 [13,14], are stable for days despite
the high reactivity of phosphite molecules in aqueous medium.
This result suggests that the coordination to metal centres,
such as ruthenium(II), stabilises these phosphorus molecules
against oxidation and hydrolysis. Indeed, the hydrolysis of
triethyl phosphite was followed in solid-state trans-[Ru(NO)(NH3)4
P(OEt)3](PF6)3 over an eight-month period and produced
trans-[Ru(NO)(NH3)4P(OH)(OEt)2](PF6)3 and ethanol [15]. A similar
behaviour was described for [Mo(CO)5P(OH)(OEt)2], which is also
hydrolysed in the solid-state to [Mo(CO)5(P(OH)3)] [16]. Despite
these observations, detailed information on the kinetics and the
mechanisms of such hydrolyses have not been reported.
the number and characteristics of the R groups [2,5–7].
The phosphites are easily oxidised by molecular oxygen, even
without a catalyst, which leads to the corresponding phosphoryl
derivatives [5,7]. In addition, these compounds are readily hydroly-
sed. The mechanism underlying this hydrolysis is an important
focus of discussion because of its importance in nucleic acid
chemistry and industrial processes [5,7]. Michaelis and Arbuzov
[8] proposed that phosphite hydrolysis occurs through the
electrophilic attack of the lone electron pair of phosphorus on
water hydrogen and the subsequent nucleophilic attack of the
water oxygen on the carbon in
a-position, which subsequently
The phosphorus(III) ligands exhibit a high trans effect and trans
influence when coordinated to metal centres. Thus, they are
notably interesting ligands for tailoring metal complexes for
⇑
Corresponding author. Tel./fax: +55 16 33739976.
E-mail address: douglas@iqsc.usp.br (D.W. Franco).
http://dx.doi.org/10.1016/j.poly.2014.06.002
0277-5387/Ó 2014 Elsevier Ltd. All rights reserved.

D.R. Truzzi, D.W. Franco / Polyhedron 81 (2014) 238–244
239
Fig. 1. Mechanisms of phosphite hydrolysis: (a) Michaelis–Arbuzov and (b) Aksnes (similar to organic ester hydrolysis). O⁄
=
18O.
specific applications [2,6]. In ruthenium nitrosyl complexes, the
triethyl phosphite coordinated to the trans-[Ru(NO)(NH3)4]3+ frag-
ment makes the reduction of the nitrosyl group accessible to bio-
0.10 mm; the number of scans was 16, the resolution was
2 cmꢀ1, and the range was 2000–1750 cmꢀ1
.
þ=NO
logical reduction (ENO
¼ ꢀ0:24 V versus SCE) and promotes a
2.2.2. Electrochemical measurements
fast liberation of nitric oxide (k–NO = 0.97 sꢀ1) [17]. In vitro and
in vivo tests that used trans-[Ru(NO)(NH3)4P(OEt)3](PF6)3 showed
that this complex promotes vasodilation [18,19] and exhibits activ-
ity against cancer cells [20], Leishmaniasis [21] and Chagas’ disease
[22]. However, the hydrolysis of the phosphorus ligand reduces the
efficacy of trans-[Ru(NO)(NH3)4P(OEt)3]3+ in biological media.
Thus, a better knowledge of the phosphorus(III) ligand hydrolysis
is required to improve the design of such complexes.
A Princeton Applied Research 264A instrument was used to
acquire the cyclic voltammetry (CV) and the differential pulse
voltammetry (DPV) data. In the electrochemical cell, a saturated-
calomel-electrode (SCE), a platinum-plate, and a glassy-carbon were
the reference, the auxiliary, and the working electrodes, respectively.
2.2.3. NMR
The 1H NMR spectra were recorded in a BRUKER AC-200
spectrometer with a proton frequency of 200.13 MHz using a
5-mm probe, 3-(trimethylsilyl)-2,20,3,30-tetradeuteropropionic acid
(TMSP-D4) as the internal reference (d = 0 ppm), and 40 scans per
spectrum. The 31P NMR spectra were acquired on an Agilent
This work aimed to better understand the changes in the reac-
tivity of phosphorus(III) compounds that are induced by coordina-
tion. Because of their properties [2], ruthenium(II) tetraammines
were selected as a model to investigate the induced reactivity
changes in the selected ligands. A series of phosphites were studied
in aqueous medium as free molecules and as ligands coordinated
to trans-[Ru(H2O)(NH3)4]2+ and trans-[Ru(NO)(NH3)4]3+ fragments.
Becausethe equatorial ammines remainunchanged, the coordina-
tion of phosphorus(III) to trans-[Ru(H2O)(NH3)4]2+ and trans-
[Ru(NO)(NH3)4]3+ offers an interesting opportunity to compare the
effects of the metal centre on the phosphorus ligand reactivity in
notably different environments. On the trans-[Ru(NO)(NH3)4]3+ frag-
400/54 Premium Shielded with
a phosphorus frequency of
161.90 MHz using a 5-mm probe and 1024 scans for each spectrum.
The internal reference was NH4PF6 salt (d = ꢀ144 ppm). The solu-
tions were degassed with argon (purified and dried) using standard
inert atmosphere techniques [27]. Spectral processing was per-
formed using the exponential function (LB = 3.0 Hz) for apodisation.
2.3. Kinetic measurements
ment where the nitrosyl (strong
p-acceptor) ispresent, themetal cen-
tre became a good -acceptor exhibiting an accentuated Ru(III)
p
The NMR kinetics experiments were performed using D2O
solutions, which were prepared with deuterated trifluoroacetic
(CF3COOD) and acetic (CD3COOD) acids to maintain the solution pH
at 1.0 and 3.0. The temperature was maintained at 25.0 0.5 °C.
The spectral processing and area calculation were performed using
the KnowItAll(R) Informatic System 8.0 software.
character and stronger ligand polarisability than on the trans-
[Ru(H2O)(NH3)4]2+ fragment (where the nitrosyl is replaced by the
water molecule), in which the metal centre is a poor p-acceptor.
2. Experimental
A first-order reaction model was used to treat the kinetic data;
thus, the rate constants (k) were calculated from the plots of
ln(A1 ꢀ At) as a function of time.
2.1. General
The chemicals used in the present study were of reagent
grade (Aldrich or Merck). And the trans-[Ru(NH3)5Cl](Cl)2 [23],
trans-[Ru(H2O)(NH3)5](PF6)2 [24], trans-[Ru(NO)(NH3)4P(OR)3](PF6)2,
where P(OR)3 = P(OiPr)3, P(OBu)3, P(OEt)3, and P(OMe)3 [17,25], and
trans-[Ru(NO)(NH3)4P(O)(OEt)2](PF6)2 [26] complexes were synthes-
ised using procedures described in the literature.
2.4. k–NO calculation [28]
NO is readily liberated from trans-[Ru(NO)(NH3)4P(III)]3+ ions
after a one-electron reduction centred on the nitrosyl ligand.
Therefore, this reaction involves a charge transfer followed by an
irreversible reaction, which enables the measurement of the rate
constants for liberation of NO (k–NO) through the Nicholson and
Shain electrochemical method [28]. In this method, the ipa/ipc
ratio is correlated with the kinetic parameter through the working
2.2. Instrumentation
2.2.1. Infrared spectroscopy
The infrared spectra in aqueous medium were recorded on a
Bomem-102 using a silicon window with a Teflon spacer of
curve of ipa/ipc as a function of k
measurements were performed using solutions with pH 2.0,
s [28]. The electrochemical

240
D.R. Truzzi, D.W. Franco / Polyhedron 81 (2014) 238–244
l
= 0.1 mol Lꢀ1, a temperature of 25 0.1 °C, and scan rates from
whereas the intensities of the peaks from diethyl phosphite
20 mV sꢀ1 to 2 V sꢀ1
.
decreased, which indicates the hydrolysis of diethyl phosphite in
this medium. A quintet at 3.94 ppm and a triplet at 1.26 ppm were
also observed because diethyl phosphite was converted to mono-
ethyl phosphite ((O)P(H)(OH)(OEt), Fig. 2b).
3. Results
Based on the decay in the area of the quintet at 4.20 ppm as a
function of time, the observed rate constant (k) for the diethyl phos-
phite molecule decay (reaction 3) in the aqueous medium at pH 3.0
and 25.0 0.5 °C was calculated to be (7.10 0.42) ꢁ 10ꢀ6 sꢀ1 (t1/
2 ꢂ 27.0 h). The diethyl phosphite molecule was also monitored at
pH 1.0, and the observed rate constant associated with the hydroly-
sis of this molecule under this condition was (1.80 0.08) ꢁ
10ꢀ4 sꢀ1 (t1/2 ꢂ 1.1 h).
3.1. P(OR)3 and (O)P(H)(OR)2 reactivity in aqueous medium
Aqueous solutions that contained triisopropyl (P(OiPr)3),
tributyl (P(OBu)3), triethyl (P(OEt)3), and trimethyl (P(OMe)3) phos-
phites were monitored using 1H NMR as a function of time at pH 3.0.
In the first spectra of these solutions, only the chemical shifts from
the corresponding dialkyl phosphite ((O)P(H)(OR)2) and alcohol
(ROH) were observed (reaction 1), which precluded a detailed
observation of the hydrolysis of the trialkyl phosphite under these
experimental conditions. Because the first spectra was recorded
after 20 min, the estimated upper limit of the half-life of P(OiPr)3,
P(OBu)3, P(OEt)3, and P(OMe)3 in an aqueous solution at pH 3.0
and 25.0 0.5 °C (reaction 1) was 1.2 ꢁ 102 s (k ꢂ 6 ꢁ 10ꢀ3 sꢀ1).
ðOÞPðHÞðOEtÞ2 þ H2O ! ðOÞPðHÞðOHÞðOEtÞ þ EtOH
ð3Þ
1H NMR was chosen for this study instead of 31P NMR because
the spectrum is readily acquired and the chemical shifts are easily
identified and sufficiently separated to calculate the area of the
individual resonances.
PðORÞ3 þ H2O ! ðOÞPðHÞðORÞ þ ROH
ð1Þ
3.2. Reactivity of P(OR)3 and P(OH)(OR)2 coordinated to the trans-
[Ru(H2O)(NH3)4]2+ fragment
The hydrolysis of diethyl phosphite ((O)P(H)(OEt)2) also was
followed in aqueous medium at pH 3.0 using 1H NMR. Fig. 2 shows
a quintet at 4.20 ppm and a triplet at 1.35 ppm, which correspond
to the CH2 and CH3 groups of the diethyl phosphite molecule,
respectively. Instead of the expected quartet, the quintet (Fig. 2a)
was observed due to the 3J coupling between 1H and 31P. A doublet
at 5.17 and 8.77 ppm also appeared in the spectrum with a
coupling constant (J) of 720 Hz, and this doublet resulted from
the 1J coupling between the 1H and 31P nuclei. This doublet is
characteristic of diethyl phosphite in the tetracoordinate form
(reaction 2) [29–31].
According to previous spectrophotometric data, trans-[Ru
(H2O)(NH3)4P(OEt)3]2+ is stable for two weeks (k < 5 ꢁ 10ꢀ7 at pH
3.0 and 25 0.1 °C) [14]. In trans-[Ru(NH3)4(P(OEt)3)2]2+, although
the hydrolysis of the coordinated triethyl phosphite is not noted, it
is observed the phosphorus ligand dissociation, which produces
trans-[Ru(H2O)(NH3)4P(OEt)3]2+ (k = 2.6 ꢁ 10ꢀ5 sꢀ1 at pH 3.0 and
25 0.1 °C [14]).
In this study, the trans-[Ru(H2O)(NH3)4P(OiPr)3]2+, trans-[Ru(H2O)
(NH3)4P(OBu)3]2+, and trans-[Ru(H2O)(NH3)4P(OH)(OEt)2]2+ com-
plexes and the phosphite molecules were investigated to deter-
mine their hydrolysis under the same experimental conditions
(at pH 3.0 and 25.0 0.5 °C).
ð2Þ
The 1H NMR spectra of trans-[Ru(H2O)(NH3)4P(OiPr)3]2+ as a
function of time exhibited a decrease in the doublet area at
1.30 ppm, which corresponds to the CH3 groups of the coordinated
triisopropyl phosphite, and an increase in the doublet area at
1.16 ppm, which corresponds to the CH3 groups of isopropanol.
This result indicates the hydrolysis of the coordinate triisopropyl
phosphite (reaction 4), which occurs with a rate constant of
k = (4.45 0.16) ꢁ 10ꢀ7 sꢀ1 (t1/2 ꢂ 18 days). Under the same exper-
imental conditions, the calculated rate constant of the trans-
[Ru(H2O)(NH3)4P(OBu)3]2+ ion hydrolysis was k = (7.36 0.21) ꢁ
10ꢀ7 sꢀ1 (t1/2 ꢂ 11 days).
In addition to the signals of the diethyl phosphite molecule, the
spectra showed a quartet at 3.64 ppm and a triplet at 1.17 ppm due
to the CH2 and CH3 groups of the ethanol molecule (Fig. 2c). This
result was confirmed by the addition of ethanol to the sample.
The intensities of the peaks from ethanol increased over time,
trans-½RuðH2OÞðNH3Þ PðORÞ ꢃ2þ þ H2O
4
3
! trans-½RuðH2OÞðNH3Þ PðOHÞðORÞ ꢃ2þ þ ROH
ð4Þ
4
2
Similar to the aquo complexes of trialkyl phosphites,
trans-[Ru(H2O)(NH3)4P(OH)(OEt)2]2+ was also hydrolysed to pro-
duce ethanol and the corresponding monoethyl phosphite complex
(reaction 5). According to the 1H NMR data, this hydrolysis occurs
with a rate constant of (4.80 0.15) ꢁ 10ꢀ7 sꢀ1 (t1/2 ꢂ 17 days) at
pH 3.0 and 25.0 0.5 °C.
trans-½RuðH2OÞðNH3Þ PðOHÞðOEtÞ ꢃ2þ þ H2O
4
2
! trans-½RuðH2OÞðNH3Þ PðOHÞ ðOEtÞꢃ2þ þ EtOH
ð5Þ
4
2
3.3. Reactivity of P(OR)3 and P(OH)(OR)2 coordinated to
trans-[Ru(NO+)(NH3)4]3+ fragment
Fig. 2. 1H NMR spectra of (a) diethyl phosphite, (b) monoethyl phosphite, and (c)
ethanol after 20 h in solution in D2O at pH = 3.0 (CD3COOD), CP(OH)(OEt)2 = 2.0 -
ꢁ 10ꢀ4 mol Lꢀ1, 25.0 0.5 °C (BRUKER AC-200).
The stabilities of the trimethyl (P(OMe)3), triethyl (P(OEt)3), tri-
isopropyl (P(OiPr)3), and tributyl (P(OBu)3) phosphites coordinated

D.R. Truzzi, D.W. Franco / Polyhedron 81 (2014) 238–244
241
to the trans-[Ru(NO)(NH3)4]3+ fragment were also evaluated in an
aqueous medium. In contrast to the results found for the free
ligands, the 1H NMR chemical shifts of these complexes and their
hydrolysis products are near one another, which made their iden-
tification and the calculation of their areas complicated. Thus, 31P
NMR was used to follow the reactions.
According to the 31P NMR spectra, trans-[Ru(NO)(NH3)4
P(OMe)3]3+ in a solution at pH 3.0 and 25.0 0.5 °C initially exhib-
ited only one peak at 85 ppm, and this peak decayed with a rate
constant of (3.01 0.05) ꢁ 10ꢀ5 sꢀ1 (t1/2 = 6.4 h). Concurrently,
the peak at 71 ppm, which is related to the trans-[Ru(NO)(NH3)4
P(OH)(OMe)2]3+ species, grew with an identical rate constant
(k = (3.03 0.05) ꢁ 10ꢀ5 sꢀ1) (Fig. 3).
The trans-[Ru(NO)(NH3)4P(OMe)3]3+ decay was also monitored
in aqueous solution at pH 3.0 using infrared spectroscopy
(Fig. 4). The initial mNO at 1922 cmꢀ1 decreased in intensity
þ
with the concurrent appearance of a new mNO at 1891 cmꢀ1 as a
þ
function of time. The isosbestic point shown in Fig. 4 also suggests
that the P(OMe)3 ligand in trans-[Ru(NO)(NH3)4P(OMe)3]3+ was
hydrolysed to quantitatively produce trans-[Ru(NO)(NH3)4P(OH)
(OMe)2]3. +
Fig. 4. Infrared spectra of trans-[Ru(NO)(NH3)4P(OMe)3]3+ in pH 3.0,
l
= 0.1 mol Lꢀ1, and 25.0 1.0 °C.
An identical behaviour was observed for the nitrosyl complexes
of triethyl, triisopropyl, and tributyl phosphite (reaction 6). The
rate constants associated with the hydrolysis of each of these
complexes at pH 3.0 and 25.0 1.0 °C are summarised in Table 1.
Table 1
Hydrolysis rate constants of phosphites that were bonded to an [Ru(NO)(NH3)4]3+
fragment at pH 3.0 and 25.0 0.5 °C.
Complex ions
k (sꢀ1
)
Reference
trans-½RuðNOÞðNH3Þ PðORÞ ꢃ3þ þ H2O
t-[Ru(NO)(NH3)4P(OMe)3]3+
t-[Ru(NO)(NH3)4P(OEt)3]3+
t-[Ru(NO)(NH3)4P(OiPr)3]3+
t-[Ru(NO)(NH3)4P(OBu)3]3+
t-[Ru(NO)(NH3)4P(O)(OH)2]2+
t-[Ru(NO)(NH3)4P(O)(OEt)2]2+
3.01 ꢁ 10ꢀ5
2.90 ꢁ 10ꢀ6
1.35 ꢁ 10ꢀ5
6.04 ꢁ 10ꢀ6
2.10 ꢁ 10ꢀ4⁄
8.90 ꢁ 10ꢀ7⁄⁄
This work
This work
This work
This work
[32]
4
3
! trans-½RuðNOÞðNH3Þ PðOHÞðORÞ ꢃ3þ þ ROH
ð6Þ
4
2
3.4. Electrochemical properties of the nitrosyl complexes of
phosphorus(III) and k–NO
[26]
Rate constant calculated for the nitrosyl complex decay as a consequence of the
phosphorus ligand isomerisation⁄ or dissociation⁄⁄
.
The biological activity of the ruthenium nitrosyl complexes is
related to their ability to release nitric oxide after a one-electron
reduction (reaction 7) and nitroxyl after a two-electron reduction
(reaction 8) [33]. Recently, the trans-[Ru(NO)(NH3)4P(OEt)3]3+ ion
was described to generate NO or HNO under controlled-reduction
medium exhibited an identical profile for all of the complexes
(Fig. 5a). The [Ru(NO+)]/[Ru(NO)] and [Ru(NO)]/[Ru(HNO)] reduc-
tion processes (reactions 7 and 8, Table 2) are clearly observed in
the differential pulse voltammogram (Fig. 5b).
þ=NO
conditions (ENO
¼ ꢀ0:10 V and ENO/HNO = ꢀ0.70 V versus SCE)
þeꢀ
3þ
[33]. This ability was also investigated in the trans-[Ru(NO)(NH3)4
2þ
trans-½RuðNOþÞðNH3Þ PðORÞ ꢃ ꢀ trans-½RuðNO3Þ PðORÞ ꢃ
ð7Þ
P(III)]n+ ions in this study. The cyclic voltammogram in an aqueous
4
3
4
3
ꢀeꢀ
trans-½RuðNOÞðNH3Þ PðORÞ ꢃ2þþ
4
3
þeꢀ
ꢀeꢀ
H3Oþ ꢀ trans-½RuðHNOÞðNH3Þ PðORÞ ꢃ2þ þ H2O
ð8Þ
4
3
Based on the rate constant data for the NO liberation (k–NO),
which was calculated for the trans-[Ru(NO)(NH3)4L]n+ series
[2,34], the k–NO value can be associated with the trans effect exhib-
ited by the ligand trans to NO. The esters of phosphorus(III) are
known to exert high trans effects; thus, a fast NO release is
expected for trans-[Ru(NO)(NH3)4L]n+, where L = P(III) [2].
Because trans-[Ru(NO)(NH3)4P(OR)3]3+ ions can be hydrolysed
at pH 5.0, which may affect the k–NO measurement associated with
reaction 9, the k–NO calculation was performed at pH 2.0 and
25.0 0.1 °C (Table 2). The k–NO values found for trans-
[Ru(NO)(NH3)4P(OEt)3]3+ at pH 5.0 (previous reported) [17] and
pH 2.0 were essentially identical within the experimental error
limits (0.97 and 0.98 sꢀ1, respectively).
k—NO
trans-½RuðNOÞðNH3Þ PðORÞ ꢃ ! trans-½RuðH2OÞðNH3Þ PðORÞ ꢃ2þ þNO
2þ
4
3
4
3
ð9Þ
The process that corresponds to HNO/NO oxidation was not
clearly observed even at high scan rate (2 V sꢀ1) and 5 °C, which
prohibited the calculation of k–HNO using the Nicholson and Shain
[28] method.
Fig. 3. trans-[Ru(NO)(NH3)4P(OMe)3]3+ in D2O at pH = 3.0 (CD3COOD) and
25.0 0.5 °C. (a) 31P NMR spectra (using NH4PF6 as the internal reference); (b)
variation in the area of the 31P NMR peaks as a function of time.

242
D.R. Truzzi, D.W. Franco / Polyhedron 81 (2014) 238–244
reasoning is consistent with the observed faster hydrolysis of
phosphites coordinated to a trans-[Ru(NO)(NH3)4]3+ fragment than
that of phosphites coordinated to
fragment.
a
trans-[Ru(H2O)(NH3)4]2+
Although the hydrolyses of the trialkyl phosphite ligands in the
trans-[Ru(H2O)(NH3)4P(OR)3]2+ and trans-[Ru(NO)(NH3)4P(OR)3]3+
species produce the respective dialkyl phosphite complexes, the
trialkyl phosphite ligands in the bisphosphito complex (trans-
[Ru(NH3)4(P(OR)3)2]2+) do not hydrolyse as long as they remain
coordinated [13,14]. Instead, the aquation of one of the trialkyl
phosphite groups is observed (k = 1.90–8.02 ꢁ 10ꢀ5 sꢀ1 at pH 3.0
and 25 1 °C for trans-[Ru(NH3)4(P(OR)3)2]2+
,
where P(OR) =
P(OiPr)3, P(OBu)3, P(OEt)3, and P(OMe)3 [13,14]). For trans-[Ru
(H2O)(NH3)4P(OH)(OEt)2]2+
, phosphite hydrolysis is observed,
whereas in trans-[Ru(NO)(NH3)4P(O)(OEt)2]2+, the deprotonated
diethyl phosphite ligand dissociates without prior hydrolysis
(Table 1) [26].
Fig. 5. trans-[Ru(NO)(NH3)4P(OMe)3]3+ ion in aqueous solution at pH 2.0,
Indeed, the phosphorus ester ligands can undergo both hydroly-
sis and dissociation. Thus, when kdiss > khyd, phosphorus(III) disso-
ciation is observed, but when kdiss < khyd, hydrolysis is observed.
The more favourable reaction (hydrolysis or dissociation) for each
complex may be related to intrinsic factors of the system, such as
the degree of susceptibility of the phosphite ligand to nucleophilic
attack and the trans effect of the ligand trans to the phosphite.
Hence, if the rate constant of the diethyl phosphite dissociation
in trans-[Ru(NO)(NH3)4P(O)(OEt)2]2+ is kdiss = 8.90 ꢁ 10ꢀ7 sꢀ1, its
l
= 0.1 mol Lꢀ1, CRu = 1.5 ꢁ 10ꢀ3 mol Lꢀ1, and T = 5 0.1 °C (a). The cyclic voltam-
mogram was obtained at a scan rate of 100 mV sꢀ1; and (b) the differential pulse
voltammogram was performed at a scan rate of 20 mV sꢀ1
.
Table 2
Electrochemical data and the calculated k–NO for some trans-[Ru(NO)(NH3)4P(III)]3+
ions at pH 2.0 and 25.0 0.1 °C.
*
*
þ =NO
ENO
estimated hydrolysis rate constant may be khyd < 8.90 ꢁ 10ꢀ7 sꢀ1
.
Complex ions
ENO/HNO
k–NO
t-[Ru(NO)(NH3)4P(OMe)3]3+
t-[Ru(NO)(NH3)4P(OEt)3]3+
t-[Ru(NO)(NH3)4P(OiPr)3]3+
t-[Ru(NO)(NH3)4P(OBu)3]3+
t-[Ru(NO)(NH3)4P(O)(OH)2]2+
t-[Ru(NO)(NH3)4P(O)(OEt)2]2+
ꢀ0.12
ꢀ0.68
0.26
0.97 [17]
2.85
0.91
0.22
Then, the stability of phosphites in nitrosyl complexes against
hydrolysis follows the sequence of P(O)(OEt)2 > P(OEt)3 >
P(OBu)3 > P(OiPr)3 > P(OMe)3. This sequence does not match the
31P NMR chemical shift sequence, which is d31P = 68, 80, 79, 75,
and 84 ppm, respectively. However, with the exception of
P(OMe)3 (d13C = 61 ppm), this sequence is consistent with the 13C
ꢀ0.10 [17]
ꢀ0.19
ꢀ0.70 [33]
ꢀ0.39
ꢀ0.10
ꢀ0.47
ꢀ0.52 [32]
ꢀ0.50 [26]
ꢀ0.79
ꢀ0.80 [26]
0.24 [26]
*
Values vs. SCE.
NMR chemical shift sequence for phosphite
a-carbon atoms,
namely d13C = 64, 70, 75, and 81 ppm (Fig. 6).
In trans-[Ru(NO)(NH3)4P(III)]3+, the phosphite is already acti-
vated by the Ru-P bond; thus, nucleophilic attack by the water
4. Discussions
molecule may be more favourable at the phosphite
a-carbon than
The free trialkyl phosphites were quickly hydrolysed in the
aqueous media at pH 3.0 and 25.0 0.1 °C. There is indeed a con-
siderable difference in the reaction time scale (from seconds to
hours) between the hydrolysis of triethyl phosphite and that of
diethyl phosphite.
Diethyl phosphite hydrolyses faster at pH 1.0 (k = (1.80
0.08) ꢁ 10ꢀ4 sꢀ1; t1/2 = 1.1 h) than at pH 3.0 (k = (7.1 0.42) ꢁ
10ꢀ6 sꢀ1; t1/2 = 27. 0 h) by forming a phosphonium salt before the
water nucleophilic attack, as suggested by the acid catalysis path-
way [35,36].
at the phosphorus atom (Fig. 7a). Therefore, the hydrolysis mech-
anism in trans-[Ru(NO)(NH3)4P(III)]3+ for P(III)
= P(O)(OEt)2,
P(OEt)3, P(OBu)3, and P(OiPr)3 (Fig. 7a) likely occurs via the Michae-
lis–Arbuzov proposal. In contrast, in the trans-[Ru(NO)(NH3)4
P(OMe)3]3+ ion, which exhibits the most positive phosphorus atom
(d31P = 84 ppm) and the smallest steric effect among the studied
All phosphites tested in this study are substantially stabilised
against hydrolysis when they are coordinated to the Ru(II) metal
centre. The triisopropyl, tributyl, and diethyl phosphites coordi-
nated to the trans-[Ru(H2O)(NH3)4]2+ fragment were found to
hydrolyse with rate constants of the same order of magnitude
(4.4–7.3 ꢁ 10ꢀ7 sꢀ1). The increased stability against hydrolysis
of the phosphite molecules coordinated to the trans-[Ru
(H2O)(NH3)4]2+ fragment may be explained by Ru(II) ? P(III)
back-bonding, which increases the electronic density on the phos-
phorus(III) ligand and deactivates this ligand against nucleophilic
attack and the consequential hydrolysis.
The extension of the Ru(II) ? P(III) back-bonding in the trans-
[Ru(L)(NH3)4P(III)]n+ compounds depends on the ligand (L) in the
position trans to the phosphorus ester. Thus, this back-bonding
tends to be smaller in nitrosyl complexes than in aquo species
because the nitrosonium ligand is a strong
the nitrosonium competes for the Ru(II) 4d
decreases the electronic density in the phosphite ligand. This
p
-acceptor. In this case,
p
electrons, which
Fig. 6. Correlation between the khyd values and d13C (ppm) for phosphite a-carbon
in a ruthenium nitrosyl complex.

D.R. Truzzi, D.W. Franco / Polyhedron 81 (2014) 238–244
243
Fig. 7. Mechanism of phosphite hydrolysis in ruthenium nitrosyl complexes: (a) O–C bond break and (b) P–O bond break.
ions, the nucleophilic attack appears more likely to occur at the
phosphorus atom, i.e., via the Aksnes mechanism (Fig. 7b).
Regarding the electrochemical properties, all five phosphite
nitrosyl complexes can selectively generate NO or HNO upon
reduction. From the first to the second reduction process, which
are centred on the nitrosonium ligand, the potential values exhib-
ited at least a 200-mV difference, which enables the selective nitr-
osonium reduction to NO or HNO according to the selected
chemical reducing or electrochemical potential applied.
The described nitrosyl complexes quickly release nitric oxide
(k–NO = 0.22 ꢀ 2.87 sꢀ1 for P(O)(OH)2 and P(OiPr)3, respectively) or
nitroxyl (kꢀ–NO ꢄ k–NO) when they are activated by reduction
centred on the nitrosyl ligand.
In summary, in addition to providing information that will
increase our knowledge of phosphorus chemistry, these findings
may be useful for tailoring new complexes for catalytic and medi-
cal applications.
The rate of NO release (k–NO
) in the aqueous medium
follows the sequence P(OiPr)3 ꢄ P(OEt)3 > P(OBu)3 ꢄ P(OMe)3 >
P(O)(OEt)2 > P(O)(OH)2. This sequence is identical to the observed
sequence for the aquation of the pyrazine ligand in trans-
[Ru(pz)(NH3)4P(III)]n+ using these phosphite molecules as ligands
Acknowledgements
The authors acknowledge FAPESP, CNPq, and CAPES from Brazil
for their financial support.
This manuscript is dedicated in memoriam of our friend and
colleague José Cardoso do Nascinemento Filho.
[2,6]. In general, an increase in the
are bonded to the phosphite -carbon substantially increases the
trans-labilising effect of this phosphite ligand. In addition,
the removal of -inductors groups that are bonded to the phos-
r-inductor groups that
a
r
References
phite oxygen, such as in diethyl phosphite and phosphorous acid,
substantially decreases the trans-labilising effect.
[1] L. Dahlenburg, Coord. Chem. Rev. 249 (2005) 2962.
[2] J.C. Toledo, B.D.S.L. Neto, D.W. Franco, Coord. Chem. Rev. 249 (2005) 419.
[3] N. Fey, A.G. Orpen, J.N. Harvey, Coord. Chem. Rev. 253 (2009) 704.
[4] P.B. Dias, M.E.M. Depiedade, J.A.M. Simoes, Coord. Chem. Rev. 135 (1994) 737.
[5] J. Kirby, S.G. Warren, The Organic Chemistry of Phosphorus, Elsevier Publishing
Company, Amterdam/London/New York, 1967.
[6] J.C.N. Filho, J.B.D. Lima, B.S.L. Neto, D.W. Franco, J. Mol. Catal. 90 (1994) 257.
[7] P.J. Murphy, Organophosphorus Reagents, 1st ed., Oxford, 2004.
[8] A.K. Bhattacharya, G. Thyagarajan, Chem. Rev. 81 (1981) 415.
[9] G. Aksnes, D. Aksnes, Acta Chem. Scand. 18 (1964) 1623.
[10] G. Aksnes, D. Aksnes, Acta Chem. Scand. 18 (1964) 38.
[11] F.H. Westheimer, S. Huang, F. Covitz, J. Am. Chem. Soc. 110 (1988) 181.
[12] W. Gerrard, W.J. Green, R.A. Nutkins, J. Chem. Soc. (1952) 4076.
[13] D.W. Franco, Inorg. Chim. Acta 48 (1981) 1.
[14] D.W. Franco, H. Taube, Inorg. Chem. 17 (1978) 571.
[15] G. Metzker, J.C. Toledo Jr., F.C.A. Lima, A. Magalhães, D.R. Cardosoa, D.W.
Franco, J. Braz. Chem. Soc. 21 (2010) 1266.
[16] C.J. Xi, Y.H. Liu, C.B. Lai, L.H. Zhou, Inorg. Chem. Commun. 7 (2004) 1202.
[17] L.G.F. Lopes, E.E. Castellano, A.G. Ferreira, C.U. Davanzo, M.J. Clarke, D.W.
Franco, Inorg. Chim. Acta 358 (2005) 2883.
[18] P.G. Zanichelli, H.F.G. Estrela, R.C. Spadari-Bratfisch, D.M. Grassi-Kassisse, D.W.
Franco, Nitric Oxide-Biol. Chem. 16 (2007) 189.
[19] A.S. Torsoni, B.F. de Barros, J.C. Toledo, M. Haun, M.H. Krieger, E. Tfouni, D.W.
Franco, Nitric Oxide-Biol. Chem. 6 (2002) 247.
[20] R.Z. Osti, F.A. Serrano, T. Paschoalin, M. Massaoka, L.R. Travassos, D.R. Truzzi,
E.G. Rodrigues, D.W. Franco, Aust. J. Chem. 65 (2012) 1333.
Although the rates of HNO release have not been directly mea-
sured, based on the absence of an anodic wave (EHNO/NO) even at
5 °C and 2 V sꢀ1, k–HNO should be higher than k–NO for all complexes
described herein.
5. Conclusion
The coordination of phosphites to ruthenium(II) centres stabi-
lises these molecules against hydrolysis. The rate of the trialkyl
phosphite hydrolysis changed from k ꢂ 6 ꢁ 10ꢀ3 sꢀ1 to k = 7.36–
4.45 ꢁ 10ꢀ7 sꢀ1 and 0.30–6.04 ꢁ 10ꢀ6 sꢀ1 when the phosphite
was coordinated to the trans-[Ru(H2O)(NH3)4]2+ and trans-
[Ru(NO)(NH3)4]3+ fragments, respectively. This increased stability
is explained by the
p-back-donation 4dp p
(RuII) ? 3d (PIII)
extension. The experimental data suggest that, with the exception
of trimethyl phosphite, the hydrolysis constant rate for phosphites
that are coordinated to trans-[Ru(NO)(NH3)4]3+ is related to the 13
C
NMR chemical shifts of the phosphite
a-carbon, which indicates
[21] J.C.M. Pereira, V. Carregaro, D.L. Costa, J.S. da Silva, F.Q. Cunha, D.W. Franco,
Eur. J. Med. Chem. 45 (2010) 4180.
that hydrolysis occurs via the Michaelis–Arbuzov mechanism.

244
D.R. Truzzi, D.W. Franco / Polyhedron 81 (2014) 238–244
[22] J.J. Silva, W.R. Pavanelli, J.C. Pereira, J.S. Silva, D.W. Franco, Antimicrob. Agents
Chemother. 53 (2009) 4414.
[30] P.R. Hammond, J. Chem. Soc. (1962) 1365.
[31] D.N. Akbayeva, M. Di Vaira, S.S. Costantini, M. Peruzzini, P. Stoppioni, Dalton
Trans. (2006) 389.
[32] D.R. Truzzi, A.G. Ferreira, S.C. da Silva, E.E. Castellano, F.D. Chagas Alves Lima,
D.W. Franco, Dalton Trans. 40 (2011) 12917.
[33] G. Metzker, E.V. Stefaneli, J.C.M. Pereira, F.D.A. Lima, S.C. da Silva, D.W. Franco,
Inorg. Chim. Acta 394 (2013) 765.
[23] L.H. Vogt, J.L. Katz, S.E. Wiberley, Inorg. Chem. 4 (1965) 1157.
[24] C.G. Kuehn, H. Taube, J. Am. Chem. Soc. 98 (1976) 689.
[25] J.C. Toledo, Aspectos da reatividade de complexos de rutênio contendo óxido
nítrico como ligante, University of Sao Paulo, São Carlos, 2004. pp. 119.
[26] D.R. Truzzi, D.W. Franco, Inorg. Chim. Acta 421 (2014) 74.
[27] D.F. Shriver, The Manipulation of Air-sensitive Compounds, McGraw-Hill, New
York, 1969.
[34] E. Tfouni, D.R. Truzzi, A. Tavares, A.J. Gomes, L.E. Figueiredo, D.W. Franco, Nitric
Oxide-Biol. Chem. 26 (2012) 38.
[28] R.S. Nicholson, I. Shain, Anal. Chem. 36 (1964) 706.
[29] J.P. Guthrie, Can. J. Chem. 57 (1979) 236.
[35] T.B. Brill, S.J. Landon, Chem. Rev. 84 (1984) 577.
[36] S.K. McIntyre, T.M. Alam, Magn. Reson. Chem. 45 (2007) 1022.