Ruthenium tetraammines as a model of nitric oxide donor compounds

Article abstract of DOI:10.1002/ejic.200300683

The nitric oxide liberation from trans-[Ru(NH₃) ₄(L)(NO)]³⁺ (where L = py, 4-pic, isn, nic, L-His, 4-Clpy, imN) after one-electron-chemical or electrochemical reduction was investigated through spectroscopic and electrochemical techniques, reaction-product analysis and quantum-mechanic calculations. These complexes can be formally viewed as a Ru^II(NO⁺) species and the reduction site is located on the NO ligand. The E° for the trans-[Ru^II(NH₃) ₄(L)(NO⁺)]³⁺/trans-[Ru^II(NH ₃)₄(L)(NO)]²⁺ redox process ranges from 0.072 V vs. NHE (nic) to -0.118 V vs. NHE (imN). The specific rate constants for NO dissociation from trans-[Ru^II(NH₃)₄(L)(NO)] ²⁺, evaluated through double-step chronoamperometry, range from 0.025 s^-1 (nic) to 0.160 s^-1 (ImN) at 25 °C. The [Ru ^IINO⁺/ Ru^IINO°] redox potential and the specific rate constant (k_-NO), key steps for designing nitrosyl complexes as NO-donor drug prototypes, proved to be controlled by a judicious choice of the ligand (L) trans to NO. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejic.200300683

FULL PAPER
Ruthenium Tetraammines as a Model of Nitric Oxide Donor Compounds
[a]
[a]
[a]
[b]
´
ˆ
Jose Carlos Toledo, Hildo A. S. Silva, Marciela Scarpellini, Vania Mori,
Ademir J. Camargo,[a] Mauro Bertotti,[b] and Douglas W. Franco*[a]
Dedicated to our friend and colleague Luiz Manoel Aleixo in memoriam
Keywords: Nitric oxide / Ruthenium / NO donor / N-heterocyclic ligands
The nitric oxide liberation from trans-[Ru(NH3)4(L)(NO)]3+
(where L = py, 4-pic, isn, nic, -His, 4-Clpy, imN) after one-
electron-chemical or electrochemical reduction was investig-
ated through spectroscopic and electrochemical techniques,
reaction-product analysis and quantum-mechanic calcula-
stants for NO dissociation from trans-[RuII(NH3)4(L)(NO)]2+
,
L
evaluated through double-step chronoamperometry, range
from 0.025 s−1 (nic) to 0.160 s−1 (ImN) at 25 °C. The [RuIINO+/
RuIINO0] redox potential and the specific rate constant (k-NO),
key steps for designing nitrosyl complexes as NO-donor drug
prototypes, proved to be controlled by a judicious choice of
the ligand (L) trans to NO.
tions. These complexes can be formally viewed as
a
RuII(NO+) species and the reduction site is located on the NO
ligand. The E° for the trans-[RuII(NH3)4(L)(NO+)]3+/trans-
[RuII(NH3)4(L)(NO)]2+ redox process ranges from 0.072 V vs.
NHE (nic) to −0.118 V vs. NHE (imN). The specific rate con-
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
positions are inert towards substitution reactions,[23] al-
lowing the control of the NO reactivity in relation to the
properties of the ligand trans to NO. This paper reports
on the activation of the trans-[Ru(NH3)4L(NO)]3ϩ species,
(where L ϭ N-heterocyclic ligands) to induce NO release
through reduction. Two main requirements for these com-
plexes to work as NO donors in biological media are: i) the
reduction potential of coordinated NO must be accessible
to biological reducing agents; ii) it is necessary to control
the dissociation of NO0 from the intermediate trans-
[Ru(NH3)4L(NO)]2ϩ. As described here, both requirements
can be fulfilled by means of a judicious choice of L.
Since the physiological roles of nitric oxide (NO) were
discovered,[1,2] a great deal of effort has been put into the
development of NO-carrier drugs.[3,4] The great affinity of
d6 and d5 low-spin-metal complexes for NO and the versa-
tility of NO on its own right as a ligand[5Ϫ7] make the nitro-
syl complexes a good alternative for such a proposal.[8,9]
Indeed, many metal complexes have been suggested as both
promising NO scavengers and NO donors.[10Ϫ17] In general,
the bonding between a d6 low-spin-metal center and NO,
which preferably assumes the MNOϩ form, is remarkably
strong.[5,6] Therefore, for tailoring NO-donor compounds,
procedures to generate MNO0 species, in which NO is lab-
ile, are essential. Strategies involving photochemistry[18,19]
and reduction activation[20] of nitrosyl complexes have been
proposed as alternatives.
Results and Discussion
The systems dealt with in this study, the trans-
[Ru(NH3)4(L)(NO)]3ϩ complex ions, are EPR silent. In ad-
dition, their νNO is always higher than 1900 cmϪ1 and the
RuϪNϪO angle obtained by X-ray crystallography is close
to 180°: trans-[Ru(NH3)4(nic)(NO)](SiF6)3 (177.0°),[21]
In this context, the photochemical[9,21,22] and reductive
pathways[9,15,16] to induce NO liberation in trans-
[Ru(NH3)4(L)(NO)]3ϩ complex ions have been explored.
This is a promising system, since these complexes are gener-
ally resistant to air oxidation and are water-soluble and ro-
bust under physiological conditions.[21,22] Furthermore, it is
well-known that ammine ligands localized in the equatorial
trans-[Ru(NH3)4(H2O)(NO)]Cl3
(178.1°),[24]
trans-
[Ru(NH3)4(4-pic)(NO)](SiF6)(BF4)·H2O (178.6°) and trans-
[Ru(NH3)4P(OEt)3(NO)](CF3COO)3 (174.9°).[25] Based on
these properties, it is reasonable to assign the [RuIINOϩ]
formula to all these trans-[Ru(NH3)4(L)(NO)]3ϩ complexes.
The result of the reaction with hydroxide ions, always yield-
ing the corresponding nitro compound,[9,21,22,26] trans-
[Ru(NH3)4(L)(NO2)]ϩ, confirms the nitrosonium character
of the NO ligand in such species.
[a]
´
Instituto de Quımica de Sa˜o Carlos, Universidade de Sa˜o Paulo,
Av. Trabalhador Sa˜oCarlense 400, 13560-970 Sa˜o Carlos, Brazil
Fax: (internat.) ϩ55-16-2739976
E-mail: douglas@iqsc.usp.br
[b]
´
Instituto de Quımica, Universidade de Sa˜o Paulo,
Av. Prof. Lineu Prestes 748, 05508900 Sa˜o Paulo, Brazil
Eur. J. Inorg. Chem. 2004, 1879Ϫ1885
DOI: 10.1002/ejic.200300683
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1879

D. W. Franco et al.
FULL PAPER
It is well-known that nitrosyl complexes in aqueous solu- havior. Furthermore, the resulting solutions are EPR silent
tion react with hydroxide ions yielding the respective nitro at liquid nitrogen temperature.
compounds (see Equation 1), depending on both the pH
The trans-[Ru(NH3)4L(NO)]2ϩ ions were generated
of the solution and the nature of L.[5,6,21,22,26] Since nitro through chemical [Cd(Hg) and EuII] or electrochemical re-
compounds are not expected to exhibit the hypotensive ef- duction. Figure 1 shows typical UV/Vis spectra for trans-
fect observed in nitrosyl complexes, the equilibrium estab- [Ru(NH3)4(py)(NO)]3ϩ, when the solution is electrolyzed in
lished between the two species, trans-[Ru(NH3)4L(NO)]3ϩ a spectroelectrochemical experiment as a function of time.
and trans-[Ru(NH3)4L(NO2)]ϩ, in physiological pH, is a The observed bathochromic shift (from λ226 and λ267 to λ256
[33]
fundamental factor to be considered when utilizing nitrosyl and λ330
)
is consistent with the lower π-acceptor ability
complexes as nitric oxide donors. According to the Keq of the NO0 ligand relative to the NOϩ ligand. The appear-
data[9,21,22,26] for Equation 1, the trans-[Ru(NH3)4L(NO)]3ϩ ance of a band at 406 nm during the experiment is in agree-
form accounts for more than 98 % of the nitrosyl complexes ment with the formation of trans-[Ru(NH3)4(py)(H2O)]2ϩ
,
at pH 7.
since this species absorbs strongly in this region (ε406 ϭ 3.4
ϫ 103 Ϫ1 cmϪ1).[32]
(1)
Cyclic voltammograms of trans-[Ru(NH3)4(L)(NO)]3ϩ
aqueous solutions show only one monoelectronic redox
process between Ϫ0.6 V and 1.0 V versus SCE,[21,22] which
was attributed to the couple RuIINOϩ/RuIINO0, in Equa-
tion (2):
(2)
DFT computation[27] for trans-[RuII(NH3)4(L)(NOϩ)]3ϩ/2ϩ
(where L ϭ NH3, ClϪ, OHϪ, py and pz), indicates that the
LUMO is always predominantly on the π* of NO (68Ϫ7
0%), although the HOMO is dependent on the nature of L:
90Ϫ95 % Ru (dxy) for L ϭ NH3, ClϪ, OHϪ and 100 % L
(πL) for L ϭ pyridine and pyrazine. Thus, the one-electron
reduction of these complexes is expected to generate
[RuIINO0] species. Indeed, the coordinated NO radical have
been detected through electron paramagnetic-resonance
spectroscopy[28] for the reduced form of the trans-
[Ru(NH3)4(H2O)(NO)]3ϩ ion. Considering the structural
and chemical similarities among all title complexes, such
behavior is expected to be general for the whole series. A
similar EPR spectrum[28] was also observed for the one-
electron reduced species of trans-[RuPP(Cl)(NO)]2ϩ PP ϭ
(C2H5)2P(CH2)2P(C2H5)2 or (C6H5)2P(CH2)2P(C6H5)2,
Figure 1. UV/Vis spectra for solutions containing trans-
[Ru(NH3)4(py)(NO)]2ϩ ions subjected to electrolysis as a function
of time (applied potential: Ϫ0.40 V vs. SCE; µ ϭ 0.1 NaCF3COO;
T ϭ 15 °C, [Ru] ϭ 5.0 ϫ 10Ϫ4 )
As expected, the chemical reduction of the trans-
[Ru(NH3)4L(NO)]3ϩ ions using EuII ions or Cd(Hg) also
produces the respective aqua species. Differential-pulse
polarographic experiments of trans-[Ru(NH3)4(py)(NO)]3ϩ
solutions show that after the addition of EuII ions (E° ϭ
Ϫ0.60 V vs. SCE), the reduction wave corresponding to the
RuIINOϩ/RuIINO0 redox process completely disappears
with the simultaneous formation of a redox wave, which
corresponds to the RuIII/RuII couple in trans-
[Ru(NH3)4(py)(H2O)]2ϩ. In addition, the IR spectrum of
the resulting solution does not show the easily identifiable
NO-stretching frequency at 1931 cmϪ1, indicating that the
NO ligand is no longer present in the ruthenium-coordi-
nation sphere.
trans-[Ru(cyclam)(Cl)(NO)]2ϩ
and
[Ru(bipy)2(Cl)-
(NO)]2ϩ [29]
.
The reduced species, trans-[Ru(NH3)4(L)(NO)]2ϩ, re-
leases NO0 according to Equation (3).
The rate-constant values for NO dissociation were deter-
mined by double-potential-step chronoamperometry (see
Table 1) and are consistent with the rate law:
(3)
d/dt [trans[Ru(NH3)4(L)(H2O)]2ϩ] ϭ k-NO [trans[Ru-
(NH3)4(L)(NO)]2ϩ
]
The presence of free NO in solution, after reduction of
According to the data shown in Table 1, the rate con-
the nitrosyl complexes, was detected by cyclic voltammetric stants for NO dissociation in trans-[Ru(NH3)4(L)(NO)]2ϩ
and differential-pulse polarographic experiments (E° NOϩ/ ions vary from 0.025 sϪ1 (isn) to 4.00 sϪ1 (imC) at 25 °C.
NO0 ϭ ϩ0.80 V vs. SCE).[30Ϫ32] The presence of the re- The sequence of k-NO as a function of L increases as fol-
sulting aqua species, trans-[Ru(NH3)4(L)(H2O)]2ϩ, was also lows: pic ഠ nic ഠ H2O ഠ py Ͻ -His ഠ imN Ͻ pz Ͻ
evident from the electronic spectra and voltammetric be- imC, which is the same sequence observed for water[34] or
1880
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Eur. J. Inorg. Chem. 2004, 1879Ϫ1885

Ruthenium Tetraammines as a Model of Nitric Oxide Donor Compounds
FULL PAPER
Table 1. Specific rate constants for NO0 dissociation from trans-[Ru(NH3)4(L)(NO)]2ϩ, [RuIINOϩ/RuIINO0] redox potential and electro-
chemical ligand parameters
I
[a]
Ion complex
k-NO (sϪ1
)
E0
(V vs. NHE)
ΣEL
(NOϩ/NO)
[b]
trans-[Ru(NH3)4(nic)(NO)]2ϩ
0.025
0.043
0.070
0.072[21]
0.052[21]
Ϫ0.008
0.56
0.54
0.51
0.54
0.32
0.53
0.42
0.40
0.61
Ϫ
[b]
trans-[Ru(NH3)4(isn)(NO)]2ϩ
[b]
trans-[Ru(NH3)4(4-pic)(NO)]2ϩ
[b]
trans-[Ru(NH3)4(4-Clpy)(NO)]2ϩ
0.030
0.012
[c]
trans-[Ru(NH3)4(H2O)(NO)]2ϩ
0.040[24]
0.060
Ϫ0.148[24]
0.012[21]
[b]
trans-[Ru(NH3)4(py)(NO)]2ϩ
[b]
trans-[Ru(NH3)4(-His)(NO)]2ϩ
0.140
0.160
Ϫ0.108[22]
Ϫ0.118[22]
0.112[21]
[b]
trans-[Ru(NH3)4(imN)(NO)]2ϩ
[b]
trans-[Ru(NH3)4(pz)(NO)]2ϩ
0.070
[c]
trans-[Ru(NH3)4 (imC)(NO)]2ϩ
4.000[20]
0.980[25]
Ϫ0.298[20]
0.142[25]
[c]
trans-[Ru(NH3)4P(OEt)3(NO)]2ϩ
0.68
[a] (µ ϭ 0.1, NaCF3COO; T ϭ 25 °C; [Ru] ϭ 1.0 ϫ 10Ϫ3 , pH ϭ 5). [b] Estimated by chronoamperometric method; most of the reported
[c]
values are the average of at least three determinations; uncertainty of Ϯ 15%. Estimated by cyclic voltammetric method (Nicholson
and Shain).
sulfate[32] lability in trans-[Ru(NH3)4L(Y)]2ϩ complexes
(where L ϭ N-heterocyclic ligand, Y ϭ H2O or SO42Ϫ).
According to the dissociative pathway for octahedral
complexes, NO labilization should reflect the affinity of the
trans-[Ru(NH3)4(L)(H2O)]2ϩ complex ions for the NO li-
gand and should be directly connected to the effective ru-
thenium charge in these complexes. Due to the similarities
of the ion complexes studied, the ruthenium effective charge
could be discussed on the basis of the electronic properties
of the trans N-heterocyclic ligands. It is well-accepted that
the higher the π-withdrawing ability of L, the more positive
the redox potential of the RuIII/II couple and, therefore, the
lower the specific rate constant for the dissociation of the
ligand leaving. Since the Mnϩ/(nϪ1)ϩ redox potential is an
indication of the metal-center-effective charge, it is expected
Ј
that the higher the trans-[Ru(NH3)4(L)(H2O)]3ϩ/2ϩ redox
Figure 2. Correlation between the k-NO values and E° trans-
[Ru(NH3)4(L)(H2O)]3ϩ/2ϩ (V vs. SCE)
potential,[35] the lower the k-NO value. Indeed, as observed
for other leaving ligands, a linear tendency (k-NO/sϪ1
ϭ
Ϫ0.7 ϫ E° trans-[Ru(NH3)4(L)(H2O)]3ϩ/2ϩ ϩ 0.07; R ϭ
0.97; pyrazine value not considered) is observed when the
trans-[Ru(NH3)4(L)(H2O)]3ϩ/2ϩ redox potential is plotted
against the k-NO values (see Figure 2). The ligand electro-
chemical parameter (EL), introduced by Lever,[36] is known
to be helpful in predicting the metal redox potential and we
expected to find a correlation between the k-NO values and
the sum of EL (ΣEL) (see Table 1). This correlation exists
and as can be observed in Figure 3 (k-NO/sϪ1 ϭ Ϫ0.81 ϫ
ΣEL ϩ 0.48; R ϭ 0.997, pyrazine value not considered).
Since EL values for a large number of N-heterocyclic li-
gands are available in the literature,[36] this correlation could
become a very convenient tool for estimating the rate con-
stants for NO dissociation from trans-[Ru(NH3)4-
(L)(NO)]2ϩ species.
As observed in Table 1, the values for NO dissociation
when L ϭ pz, imC and P(OEt)3 do not follow the trend Figure 3. Correlation between the k-NO values and ΣEL (ΣEL ϭ 4
ϫ EL NH3 ϩ EL L)
observed for the other N-heterocyclic ligands (see Figure 3).
The imC and P(OEt)3 properties differ substantially from
the N-based ligands as they are coordinated through car- complexes do not fit the correlation implied by Figure 3
bon and phosphorus atoms, respectively. The trans labiliz- [imC and P(OEt)3 values were omitted for clarity]. The be-
ing effect of these two ligands is notable and therefore their havior of the pyrazine ligand has not yet been understood
Eur. J. Inorg. Chem. 2004, 1879Ϫ1885
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1881

D. W. Franco et al.
FULL PAPER
and is currently under investigation in our laboratory. How- species where L is a π-acid and should reflect the strength
ever, the same behavior has been observed for pyrazine de- of the RuϪNO bond in both species. To investigate the ori-
rivatives in studies on sulfate dissociation from trans- gin of this different behavior, DFT computations for trans-
[Ru(NH3)4(L)(SO4)] (L ϭ N-heterocyclic ligands).[32]
[Ru(NH3)4(L)(NO)]3ϩ and trans-[Ru(NH3)4(L)(NO)]2ϩ
From the discussion above, it is clear that the [RuIINOϩ/ (L ϭ py) were performed. The results obtained in terms of
RuIINO0] reduction potential is one of the key steps in acti- bond lengths and bond angles are similar to those reported
vating nitrosyl complexes to release NO. If the target is to for the two systems:[40] [Ru(CN)5(NO)]2Ϫ and
tailor a compound that can be activated in vivo through [Ru(CN)5(NO)]3Ϫ [41] [Ru(NH3)5(NO)]3ϩ and [Ru(NH3)5-
,
reduction, the [RuIINOϩ/RuIINO0] redox potential must be (NO)]2ϩ (Table 2).
in a range suitable to reducing agents present in the biologi- The MO composition (see Table 3) for trans-
cal medium. The [RuIINOϩ/RuIINO0] redox potential for [Ru(NH3)4(L)(NO)]3ϩ shows that the π interaction between
the nitrosyl complexes dealt with here (Table 1) ranges from RuII and NOϩ consists of a combination of the filled dxy
Ϫ0.118 for L ϭ imN to 0.072 V vs. NHE for L ϭ nic, and dxz orbitals (Ru) and the double degenerate, empty π*
suggesting that all these complexes could be reduced by bio- orbitals of nitric oxide besides the py* orbitals of pyridine:
logical reducing agents[37] such as NADH, the flavin co- HOMO-5 (Ru dxy 33 %, NO py 11 %, py py 54 %) and
enzymes FADH2 and FMNH2 and iron sulfur proteins. Re- HOMO-6 (Ru dxz 69 %, NO pz 22 %, py pz 6 %). Figure 4
cent
studies
have
suggested
that
the
trans- (left) shows the HOMO-6 graphical representation of trans-
[Ru(NH3)4P(OC2H5)3(NO)]3ϩ nitrosyl complex can be re- [Ru(NH3)4(py)(NO)]3ϩ. The percentage [11Ϫ22 % (π* NO)]
duced by mitochondrial reducing power[38] and that this in the HOMO-5 and HOMO-6 orbitals is consistent with
compound exhibits an effective hypotensive effect in the well-known back bonding from RuII to NOϩ, while 54
mice.[15,16] This biological activity is attributed to its NO- % for py (py) in the HOMO-5 orbital, which could be con-
donor ability. The [RuIINOϩ/RuIINO0] redox potential for sidered responsible for the influence of the trans ligand on
trans-[Ru(NH3)4L(NO)]3ϩ complexes was shown to be sen- the NO electronic density, is reflected on the [RuIINOϩ/
sitive to the nature of the ligand L, trans to NO. This was RuIINO0] redox potential and νNO, as observed.
expected, since the most accessible site for reduction in
As expected, the LUMO and LUMOϩ1 for the trans-
these complexes is localized on the nitrosyl ligand. Thus, [Ru(NH3)4(L)(NO)]3ϩ complexes [an example of these mo-
the NO electronic density and therefore the [RuIINOϩ/ lecular orbitals is shown in Figure 4 (right)] are antibonding
RuIINO0] redox potential are a function of the competition with relation to the RuϪNO π-bond. These π-antibonding
between the axial ligands, NO and L, on the ruthenium 4dπ orbitals are predominantly on NO π* (66Ϫ69 %) (Table 3),
electron density. Indeed, a correlation between the trans- which is in agreement with the formation of trans-
[Ru(NH3)4L(NO)]3ϩ/2ϩ and the respective aqua species [Ru(NH3)4(L)(NO)]2ϩ
as
a
result
of
trans-
trans-[Ru(NH3)4L(H2O)]3ϩ/2ϩ redox potential was ob- [Ru(NH3)4(L)(NO)]3ϩ one-electron reduction and with the
served. In addition, a linear correlation was also observed additional electron occupying one of these π* MOs. Indeed,
plotting the trans-[Ru(NH3)4L(NO)]3ϩ/2ϩ redox potential a similar DFT MO calculation performed on trans-
and the ligand electrochemical parameters ΣEL (Table 1) for [Ru(NH3)4(L)(NO)]2ϩ agrees with this prediction and the
L ϭ N-heterocyclic ligands.[39] This correlation is valuable singly occupied MO (HOMO) and the LUMO, which
since EL is available in the literature and was proved correspond to the LUMO and LUMOϩ1 of trans-
to be useful in previously estimating the trans- [Ru(NH3)4(L)(NO)]3ϩ
,
respectively, are composed of
[Ru(NH3)4L(NO)]3ϩ/2ϩ redox potential.
HOMO Ru (dxz) 35 %, NO (pz) 50 % and py (pz) 13 % and
It is important to stress that, depending on the electronic LUMO Ru (dxy) 28 %, NO (py) 70 % and py (py) 2 %. As
characteristics of L, the latter could be displaced instead of expected from previous DFT calculations for the
NO. In complexes where ClϪ is localized trans to NO,[24,25] [Ru(CN)5(NO)]3Ϫ and [Ru(NH3)5(NO)]2ϩ systems,[40,41]
a
as in trans-[Ru(NH3)4(Cl)(NO)]ϩ, trans-[Ru(cyclam)- pronounced bend of 139° in the RuϪNϪO angle is ob-
(Cl)(NO)]ϩ and trans-[Ru(dppe)(Cl)(NO)]ϩ, chloride is served (Table 2). Although, a π-bonding interaction be-
preferentially released before NO.
tween Ru and NO still exists, that is, HOMO-3 and
In contrast to the inertia of the RuIINOϩ species, the HOMO-4 [see Table 4 and an orbital representation in Fig-
lability of NO in RuIINO0 species seems to be common in ure 5 (left)], this RuϪNϪO bending induces a considerable
Table 2. Selected theoretical bond lengths and angles calculated by DFT for (nitrosyl)ruthenium complexes
˚
˚
Complex
RuϪNO (A)
NϪO (A)
RuϪNϪO (deg)
Ref.
trans-[Ru(NH3)4(py)(NO)]3ϩ
trans-[Ru(NH3)4(py)(NO)]2ϩ
trans-[Ru(NH3)4(nic)(NO)]3ϩ
trans-[Ru(NH3)5(NO)]3ϩ
trans-[Ru(NH3)5(NO)]2ϩ
[Ru(CN)5(NO)]3ϩ
1.820
1.910
1.775
1.808
1.894
1.770
1.893
1.130
1.174
1.137
1.153
1.216
1.176
1.221
180.0
139.0
179.4
172.8
137.1
180.0
144.9
this work
this work
[42]
[40]
[40]
[41]
[41]
[Ru(CN)5(NO)]2ϩ
1882
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Eur. J. Inorg. Chem. 2004, 1879Ϫ1885

Ruthenium Tetraammines as a Model of Nitric Oxide Donor Compounds
FULL PAPER
Table 3. Selected MO contribution in percentage for trans-[Ru(NH3)4(py)(NO)]3ϩ
trans-[Ru(NH3)4(py)(NO)]3ϩ
eV
symm
Ru
NO
NH3
L
LUMO
HOMO
Ϫ15.2
Ϫ15.2
Ϫ18.3
Ϫ18.8
Ϫ19.7
Ϫ20.2
Ϫ20.5
Ϫ20.6
π*
π*
23 (dxy
26 (dxz)
0
)
66 (py)
69 (pz)
0
5 (pz)
1
5 (s)
11 (py)
22 (pz)
3
4
4
4
4
1
3
4
8 (py)
1
HOMO-1
HOMO-2
HOMO-3
HOMO-4
HOMO-5
HOMO-6
nonbonding
nonbonding
nonbonding
π*L
π
96 (pz)
87 (pz)
25 (s)
71 (px)
54 (s,px,py)
6 (pz)
4 (dxz)
2
2
2
)
68 (dz ,dx Ϫy
2
2
)
23 (dx Ϫy
33 (dxy
69 (dxz)
)
π
MOs for trans-[Ru(NH3)4(L)(NO)]3ϩ (LUMO and
LUMOϩ1, respectively), assume a partial bonding charac-
ter, they do not seem to be strong enough to keep the metal-
coordination sphere intact, as observed. The calculated
RuϪNO bond lengths for trans-[Ru(NH3)4(L)(NO)]3ϩ (1.82
2ϩ
˚
˚
A) and trans-[Ru(NH3)4(L)(NO)] (1.91 A) are in agree-
ment with the RuϪNO bond weakening (Table 2) and they
are accompanied by a measurable lengthening of the NϪO
Figure 4. Molecular orbital description of a (nitrosyl)metal com-
plex; (left) HOMO-6: ligand π interaction between Ru (either dxy
and dxz) and NO π* orbitals (py* and pz*); (right) LUMO: antili-
gand π interaction between Ru (either dxy and dxz) and the NO π*
orbitals (py* and pz*)
˚
˚
bond, from 1.130 A to 1.174 A (Table 2), which is consist-
ent since the HOMO for the trans-[Ru(NH3)4(py)(NO)]2ϩ
ion has a considerable population and its composition is
predominant on NO π* orbitals. As shown in Table 2,
RuϪNO and NϪO bond lengthening is usual as the same
is also observed for [Ru(CN)5(NO)]3Ϫ and [Ru(NH3)5-
(NO)]2ϩ systems.[40,41]
reduction of Ru and NO π-bonding [compare Figure 4 (left)
and 5 (left)].
As a consequence, RuϪNO bond weakening is expected
and it is comprehensible that the nitric oxide ligand is much
more susceptible to dissociation in the trans-
[Ru(NH3)4(L)(NO)]2ϩ species than in the the oxidized ana-
logues. Although, the HOMO and the LUMO for trans-
[Ru(NH3)4(L)(NO)]2ϩ ions, which were totally antibonding
Conclusion
The trans-[Ru(NH3)4L(NO)]3ϩ complex ions are better
described as formally RuIINOϩ and they are stable towards
substitution reactions. Following activation by one-electron
reduction, species having a labile NO0 ligand are produced,
which makes these compounds good NO-donor drug
prototypes.
The rate of NO dissociation from the trans-
[Ru(NH3)4(L)(NO)]2ϩ and the trans-[Ru(NH3)4L(NO)]3ϩ/2ϩ
redox potential, could be modulated by a judicious choice
of the ligand, L. These two critical steps for NO-donor-
drug designing can be predicted by plots of k-NO versus ΣEL
and from the trans-[Ru(NH3)4L(NO)]3ϩ/2ϩ redox potential
versus ΣEL, respectively.
Figure 5. Molecular orbital interaction in a bent (nitrosyl)metal
complex; (left) HOMO-3: bending the NO ligand minimizes the
overlap between the metal orbitals (either dxy and dxz) and the NO
π* orbitals (either py* and pz*); (right) HOMO: the antibonding
character presents a compensatory bonding interaction between the
NO (pz*) and the metal (dxz) orbitals as RuϪNϪO bend
Table 4. Selected MO contribution in percentage for trans-[Ru(NH3)4(py)(NO)]2ϩ
trans-[Ru(NH3)4(py)(NO)]ϩ2
eV
symm
Ru
NO
NH3
L
LUMO
HOMO
HOMO-1
HOMO-2
HOMO-3
HOMO-4
HOMO-5
Ϫ9.7
Ϫ12.9
Ϫ14.1
Ϫ14.5
Ϫ14.5
Ϫ14.5
Ϫ15.3
π*
π*
28 (dxy
)
70 (py)
50 (pz)
0
0
2
5
3
2
3
2
2 (py)
13 (py)
8
97 (pz,py)
28 (pz)
19 (py,px)
68 (pz)
35 (dxz)
2
2
2
)
nonbonding
nonbonding
π
π
87 (dz ; dx Ϫy
0
0
44 (dxz)
26 (pz)
20 (py)
6 (pz)
58 (dxy
)
π*L
24 (dxz)
Eur. J. Inorg. Chem. 2004, 1879Ϫ1885
www.eurjic.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1883

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[4]
Experimental Section
Chemicals and Reagents: High purity chemicals (Aldrich) were used
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measurements
were
performed
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reading the manuscript and the Brazilian foundations FAPESP
(processes numbers 1999/07109Ϫ9, 99/11252Ϫ1 and 01/08563Ϫ7),
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