Light-Activated generation of nitric oxide (NO) and sulfite anion radicals (SO3-) from a ruthenium(ii) nitrosylsulphito complex

Article abstract of DOI:10.1039/c9dt01432b

This manuscript describes the preparation of a new Ru(ii) nitrosylsulphito complex, trans-[Ru(NH₃)₄(isn)(N(O)SO₃)]⁺ (complex 1), its spectroscopic and structural characterization, photochemistry, and thermal reactivity. Complex 1 was obtained by the reaction of sulfite ions (SO₃^2-) with the nitrosyl complex trans-[Ru(NH₃)₄(isn)(NO)]³⁺ (complex 2) in aqueous solution resulting in the formation of the N-bonded nitrosylsulphito (N(O)SO₃) ligand. To the best of our knowledge, only four nitrosylsulphito metal complexes have been described so far (J. Chem. Soc., Dalton Trans., 1983, 2465-2472), and there is no information about the photochemistry of such complexes. Complex 1 was characterized by spectroscopic means (UV-Vis, EPR, FT-IR, ¹H-and ¹⁵N-NMR), elemental analysis and single-crystal X-ray diffraction. The X-ray structure of the precursor complex 2 is also discussed in the manuscript and is used as a reference for comparisons with the structure of 1. Complex 1 is water-soluble and kinetically stable at pH 7.4, with a first-order rate constant of 3.1 × 10^-5 s^-1 for isn labilization at 298 K (t_1/2 ～ 373 min). Under acidic conditions (1.0 M trifluoroacetic acid), 1 is stoichiometrically converted into the precursor complex 2. The reaction of hydroxide ions (OH^-) with 1 and with 2 yields the Ru(ii) nitro complex trans-[Ru(NH₃)₄(isn)(NO₂)]⁺ with second-order rate constants of 2.1 and 10.5 M^-1 s^-1 (at 288 K), respectively, showing the nucleophilic attack of OH^- at the nitrosyl in 2 (Ru-NO) and at the nitrosylsulphito in 1 (Ru-N(O)SO₃). The pK_a value of the-SO₃ moiety of the N(O)SO₃ ligand in 1 was determined to be 5.08 ± 0.06 (at 298 K). The unprecedented photochemistry of a nitrosylsulphito complex is investigated in detail with 1. The proposed mechanism is based on experimental (UV-Vis, EPR, NMR and Transient Absorption Laser Flash Photolysis) and theoretical data (DFT) and involves photorelease of the N(O)SO₃^- ligand followed by formation of nitric oxide (NO) and sulfite radicals (SO₃^-, sulfur trioxide anion radical).

Full text of DOI:10.1039/c9dt01432b

Dalton
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Light-activated generation of nitric oxide (NO) and
•−
sulfite anion radicals (SO3 ) from a ruthenium(II)
Cite this: DOI: 10.1039/c9dt01432b
nitrosylsulphito complex†‡
Antonio C. Roveda, Jr., *a Willy G. Santos,a Maykon L. Souza,a Charles N. Adelson,b
d
Felipe S. Gonçalves, a Eduardo E. Castellano,c Claudio Garino,
a
Douglas W. Francoa and Daniel R. Cardoso
*
This manuscript describes the preparation of a new Ru(II) nitrosylsulphito complex, trans-[Ru(NH3)4(isn)
(N(O)SO3)]+ (complex 1), its spectroscopic and structural characterization, photochemistry, and thermal
reactivity. Complex 1 was obtained by the reaction of sulfite ions (SO32−) with the nitrosyl complex trans-
[Ru(NH3)4(isn)(NO)]3+ (complex 2) in aqueous solution resulting in the formation of the N-bonded nitro-
sylsulphito (N(O)SO3) ligand. To the best of our knowledge, only four nitrosylsulphito metal complexes
have been described so far (J. Chem. Soc., Dalton Trans., 1983, 2465–2472), and there is no information
about the photochemistry of such complexes. Complex 1 was characterized by spectroscopic means
1
(UV-Vis, EPR, FT-IR, H- and 15N-NMR), elemental analysis and single-crystal X-ray diffraction. The X-ray
structure of the precursor complex 2 is also discussed in the manuscript and is used as a reference for
comparisons with the structure of 1. Complex 1 is water-soluble and kinetically stable at pH 7.4, with a
first-order rate constant of 3.1 × 10−5 s−1 for isn labilization at 298 K (t1/2 ∼ 373 min). Under acidic con-
ditions (1.0 M trifluoroacetic acid), 1 is stoichiometrically converted into the precursor complex 2. The
reaction of hydroxide ions (OH−) with 1 and with 2 yields the Ru(II) nitro complex trans-[Ru(NH3)4(isn)
(NO2)]+ with second-order rate constants of 2.1 and 10.5 M−1 s−1 (at 288 K), respectively, showing the
nucleophilic attack of OH− at the nitrosyl in 2 (Ru–NO) and at the nitrosylsulphito in 1 (Ru–N(O)SO3). The
pKa value of the –SO3 moiety of the N(O)SO3 ligand in 1 was determined to be 5.08 0.06 (at 298 K).
The unprecedented photochemistry of a nitrosylsulphito complex is investigated in detail with 1. The
proposed mechanism is based on experimental (UV-Vis, EPR, NMR and Transient Absorption Laser Flash
Received 4th April 2019,
Accepted 25th June 2019
−
DOI: 10.1039/c9dt01432b
Photolysis) and theoretical data (DFT) and involves photorelease of the N(O)SO3 ligand followed by
rsc.li/dalton
formation of nitric oxide (NO•) and sulfite radicals (SO3•−, sulfur trioxide anion radical).
has been associated with several physiological conditions,
such as the enhancement and suppression of nitrite-depen-
Introduction
Although the sulfite ion (SO32−) is potentially toxic to living dent NO• production in the stomach,2a skin and respiratory
2−
cells, this species is widely applied as an antioxidant and pre- tract health, and anaphylactic reactions.2b SO3 is metab-
servative in food and beverages,2 and its chemistry has olized by the enzyme sulfite oxidase,3c,4 for which deficiency
received increasing attention in the last few years.2b,3 The may be lethal to humans. Most of the SO3 toxicity is related
2−
2−
SO3 anion influences the metabolism of thiocyanate (SCN−) to the production of SOX anion radicals, formed through chain
and nitrite (NO2−) in the human saliva and stomach,2a and propagation steps (eqn (1)–(4)):3d,5
2ꢀ
SO3 ! SO3•ꢀ þ eꢀ
ð1Þ
ð2Þ
aSão Carlos Institute of Chemistry, University of São Paulo, CEP 13560-970
São Carlos, SP, Brazil. E-mail: acroveda@usp.br, drcardoso@usp.br
bDept. of Chemistry, Stanford University, CA, USA
SO3•ꢀ þ O2 ! ꢀO3SOO• k ¼ 1:5 ꢁ 109 Mꢀ1 sꢀ1
cSão Carlos Institute of Physics, University of São Paulo, São Carlos, SP, Brazil
dDept. of Chemistry and NIS Interdepartmental Centre, University of Turin, Italy
†This paper is dedicated in memoriam of Prof. Dr Douglas Wagner Franco.
‡Electronic supplementary information (ESI) available: Complimentary charac-
terization and reactivity data are provided. CCDC 1915847 and 1922883. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c9dt01432b
2–
2ꢀ
ꢀO3SOO• þ SO3 ! SO4•ꢀ þ SO4
k ¼ 1:3 ꢁ 107 Mꢀ1 sꢀ1 ð3Þ
k > 2 ꢁ 109 Mꢀ1 sꢀ1 ð4Þ
2ꢀ
•ꢀ
SO4•ꢀ þ SO3 ! SO42ꢀ þ SO3
Oxidation of SO3 yields the sulfite anion radical (SO3•−),
2−
eqn (1), which in the presence of O2 reacts to form the
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oxygen-centered radicals, peroxymonosulfate radical anion by the reaction of the Ru(II) nitrosyl complex trans-
(SO5•−) and sulfate radical anion (SO4•−), eqn (2)–(4). Recent [Ru(NH3)4(isn)(NO)]3+ (complex 2 in Fig. 1) with SO32−, eqn (5):
•−
studies showed that SO3
oxidation of SO3
could be produced through
trans-½RuðNH3Þ ðisnÞðNOÞꢂ3þ þ SO3
2ꢀ
2−
4
by prostaglandin H synthase, myelo-
! trans-½RuðNH3Þ ðisnÞðNðOÞSO3Þꢂþ
ð5Þ
peroxidase, human eosinophil peroxidase and cytochrome
4
•−
•−
c.3b–f SO3 and SO5 are mild oxidants (E° = 0.63 V and
1.1 V vs. NHE at pH 7, respectively),5b,6 but are precursors of
the sulfate radical anion (SO4•−) (eqn (1)–(4)), a strong
oxidant (E° = 2.5–3.1 V vs. NHE)5b,7 comparable to the
The family of trans-[Ru(NH3)4(L)(NO)]3+ complexes is well
known to be kinetically stable and water-soluble,15 supporting
the choice of this type of nitrosyl as the synthetic precursor of
complex 1. As expected, 1 is water-soluble and kinetically
•−
hydroxyl radical.8 Due to its oxidizing strength, SO4 has
−
stable at pH 7.4 (at 298 K), and the N(O)SO3 ion is stabilized
been widely studied and recently applied in advanced oxi-
dation process technologies,9 DNA damage10 and organic
synthesis.11
upon coordination to Ru(II), making studying its reactivity
possible. The solubility and stability of 1 in water are higher
than those of all four previously reported complexes
[L5M–N(O)SO3]n (M = Fe, Ru). Our investigations on 1 also con-
tribute to a current interesting topic in the chemistry of nitro-
syl complexes and sulfur nucleophiles,16 and of S,N,O
species.16c,17 Moreover, the light-triggered generation of
the relevant radicals (NO• and SO3•−) from 1 may find utility
in many important redox and photochemical based
applications.18
−
Analogously to SO32−, the NO2 ion is also used as an anti-
oxidant and preservative in food and beverages,2a and the reac-
tion between these ions is argued to produce the somewhat
−
elusive nitrososulfonate ion (OvN–SO3
, described from
herein as N(O)SO3−) in the human stomach.2a N(O)SO3− is con-
sidered an intermediate of several nitrogen reactive
species,2a,12 such as nitric oxide (NO•), hydroxyimidogen (NOH)
−
and hyponitrous acid (H2N2O2). Furthermore, the N(O)SO3
ion has also been proposed as an intermediate in the Raschig
synthesis of hydroxylamine.1,12,13 Nevertheless, little is known
about the chemistry and physical properties of N(O)SO3−. The
only compounds isolated and characterized are the N-bonded
derivative species generated by the Boedeker Reaction,
Results and discussion
X-ray crystallography and Infrared spectroscopy
The reaction of the nitrosyl complex trans-[Ru(NH3)4(isn)
i.e. the nitrosylsulphito complexes [Fe(CN)5N(O)SO3]4− 13,14
,
(NO)]3+ (2) with SO3 (eqn (5)) yields the new nitrosylsulphito
2−
ion complex trans-[Ru(NH3)4(isn)(N(O)SO3)]+ (1), Fig. 1, a green
solid. This reaction occurs through the nucleophilic addition
of the sulfite ion to the nitrogen atom of the nitrosyl moiety
(Ru–NO) of complex 2. Complex 1 was characterized by
elemental analysis and by several spectroscopies, and the
experimental data correlated well with the DFT calculations
(see the ESI‡).
The crystal structures of 1 and of its synthetic precursor (2)
are shown in Fig. 1. Table 1 shows the main bond lengths and
angles for 1, 2 and for a previously described nitrosylsulphito
complex, cis-[RuCl(bipy)2N(O)SO3] (3).1
[RuCl(py)4N(O)SO3] (py = pyridine) and cis-[RuX(bipy)2N(O)SO3]
(X = Cl− or Br−, bipy = 2,2′-bipyridine),1 of which, only the
structure of cis-[RuCl(bipy)2N(O)SO3] has been crystallographi-
cally characterized.1 The reactivity of these complexes has not
yet been fully studied mainly owing to their insolubility and
instability.1 Moreover, the photochemistry of the N(O)SO3− ion
and the related nitrosylsulphito complexes has never been
described.
−
Herein we describe the reactivity of N(O)SO3 coordinated
to a Ru(II) complex, trans-[Ru(NH3)4(isn)(N(O)SO3)]+ (complex
1, isn = isonicotinamide), Fig. 1. This complex was synthesized
Table 1 Selected bond lengths and angles for the complexes trans-
[Ru(NH3)4(isn)(N(O)SO3)]+ (1), trans-[Ru(NH3)4(isn)(NO)]3+ (2) and cis-
[RuCl(bipy)2N(O)SO3] (3)
Ru complex
1 a
2 a
3 b
Distances (Å)
Ru–N
N–O
N–S
̲
(N̲
̲
1.877(3)
1.244(5)
1.844(4)
2.167(3)
2.12
1.750(3)
1.119(4)
—
2.099(3)
2.10
1.904(14)
1.208(17)
1.820(15)
—
Ru–Nisn
Ru–NH3
c
—
Angles (°)
Ru–N–O
Ru–N–S
O–N–S
124.4(4)
125.2(19)
110.4(3)
175.4(3)
—
—
123.8(12)
127.9(7)
108.0(11)
—
Fig. 1 X-ray and molecular structures of complexes (A) 1 and (B) 2. The
numbers in red show the bond lengths, and in blue, the angles.
Ellipsoids at 50% probability; H omitted for clarity.
Nisn–Ru–N
̲
(N̲
̲
178.32(14)
177.39(12)
a This work. b Ref. 1. c Average of the four Ru-NH3 bonds.
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Table 2 Main vibrational bands (cm−1) and assignments for a series of [L5M–(N(O)SO3)]n complexes1 and for complex 2
Assignmenta
Complex
ν(N–O)
νasym (S–O)
νsym (S–O)
νsim (S–O)
δasym (O–N–S)
δasym (O–S–O)
trans-[Ru(NH3)4(isn)(N(O)SO3)]+ (1)b
trans-[Ru(NH3)4(isn)(NO)]3+ (2)b
cis-[RuCl(bipy)2(N(O)SO3)] (3)a
cis-[RuBr(bipy)2(N(O)SO3)]a
trans-[RuCl(py)4(N(O)SO3)]a
Cs4[Fe(CN)5(N(O)SO3)]a
1366s
1933s
1370s
1372s
1346s
1357s
1263sh
—
1267sh
1270sh
1273sh
1252s
1225s
—
1250s
1255s
1258s
1229s
1040s
—
1038s
1040s
1031s
1041s
778m
—
775
775
770
623s
—
612
605s
604
621s
758w
a Ref. 1. b This work; s = strong; m = medium; w = weak; sh = shoulder.
In both complexes 1 and 2 (Fig. 1), the aromatic moiety of 0.04 Å and 3° for the bond lengths and angles, respectively,
the isn ligand is perpendicular to the plane formed by the four Table 1. Therefore, despite considerable differences in the
nitrogens of the equatorial ammines (NH3) and bisects two coordination spheres of 1 and 3, there were no significant dis-
opposite N–Ru–N angles of NH3. The Nisn–Ru–NN(O)SO bond crepancies among the bond angles and bond distances of the
3
angle in 1 is almost linear and very close to that observed for [Ru–N(O)SO3] fragments in these complexes.
the Nisn–Ru–NNO bond angle in 2 (Table 1). Complexes 1 and 2
The FT-IR spectra of 1 and 2 are shown in Fig. S1 (ESI‡) and
have slightly different Ru–NH3 bond distances (Table 1). The the main IR frequencies of the complexes 1, 2, [Fe(CN)5N(O)
Ru–N(O)SO3 bond length in 1 is ∼0.24 Å shorter than the SO3]4–, [RuCl(py)4N(O)SO3] and cis-[RuX(bipy)2N(O)SO3] (X =
average of the four Ru–NH3 distances (Table 1), showing an Cl− or Br−)13,14 are shown in Table 2. The ν(NO) observed for 2
increase in the bond order in Ru–N(O)SO3 relative to Ru–NH3 at 1933 cm−1 was shifted to 1366 cm−1 on 1 (Table 2, and
due to π interactions in the former. A similar behavior is Fig. S1 ESI‡). This shift is consistent with the weakening of the
observed for complex 2. However, the Ru–NO bond length in 2 N–O bond in 1 (1.24 Å) in comparison with 2 (1.12 Å) (Fig. 1
is ∼0.13 Å shorter than the Ru–N(O)SO3 bond length in 1 and Table 1). All the IR bands observed for the nitrosylsulphito
(Fig. 1 and Table 1). This indicates a stronger back-bonding of complexes showed similar frequencies for the N(O)SO3 moiety,
the NO ligand in 2 than that of the N(O)SO3 ligand in 1. This with differences lower than 30 cm−1 (Table 2). These data
result is consistent with the Ru–N–O angle, which is close to revealed that the vibrational frequencies of the N(O)SO3 moiety
linear in 2 (175.4°) and is 124.4° in 1 (Fig. 1). The linear angle were not strongly affected by modifications in the coordination
of Ru–N–O provides a greater overlap of the Ru dπ orbital with sphere of the complexes, in agreement with the X-ray results as
the π* orbital of NO19 in 2, and consequently, a stronger Ru– discussed above for 1 and 3.
NO bond in 2 than the Ru–N(O)SO3 bond in 1.
Electronic structure, 1H- and 15N-NMR, and EPR spectroscopy
The longer Ru–Nisn bond length in 1 than in 2 (Fig. 1 and
Table 1) shows a stronger trans-influence of the N(O)SO3 Complex 1 has two doublets in the 1H-NMR spectra with
ligand than that of the NO ligand, regarding isn in the trans chemical shifts (δ) at δ = 8.87 and 8.13 ppm (Fig. S2, ESI‡),
position. Furthermore, the S–N bond length of ∼1.84 Å for the assigned respectively to the ortho and meta hydrogens of the
N(O)SO3 ligand in 1 is ca. 10% longer than that of other S–N isn ligand in 1. The 15N NMR spectrum of 1 only exhibits one
compounds, e.g. nitrosopersulfide (SSNO−) and thionitrite peak at δ = 192.8 ppm (Fig. S3, ESI‡). The sharp narrow-width
(SNO−), 1.689 Å and 1.707 Å, respectively.16c It is also longer peaks observed in the H-NMR spectrum and the lack of EPR
1
than S-nitrosothiols coordinated to transition metal signals (EPR silent at 77 K) are consistent with a S = 0 ground
complexes.16g,h
state of 1, in agreement with the electronic structure descrip-
The Ru–N–O and Ru–N–S angles in 1 (124.4° and 125.2°, tion for the parent precursor nitrosyl complex 2, and for the
respectively) are slightly different from those reported for a family of trans-[Ru(NH3)4(L)(NO)]3+ complexes.15,22
closely related complex, trans-[Ru(NH4)P(OEt)3(NO2)](PF6), in
Nucleophilic attack at coordinated nitrosyls in ruthenium
which the Ru–N–O angle is 120.9° for one of the oxygen atoms and iron complexes is well documented in the literature.16a,23
of the NO2 ligand, and 121.4° for the other.20 The Ru–N–O, In the case of the family of trans-[Ru(NH3)4(L)(NO)]3+ com-
Ru–N–S and O–N–S angles in 1 are close to those reported for plexes, nucleophilic attack of OH− or of thiols occurs on the
S-nitrosothiols coordinated to transition metal complexes.16g,h nitrosyl ligand (Ru–NO) and leads to species with an intense
For the N(O)SO3 ligand in 1, the S–O bond lengths are shorter and broad band in the long-wave UV and visible ranges of the
than those in sodium sulfite (Na2SO3), ∼1.40 Å and 1.53 Å, spectra.16a,f,i,24 This behavior is consistent with the electronic
respectively. However, the O–S–O angles are larger in 1 than absorption band observed for 1 at λmax = 363 nm (Fig. 2)
those in Na2SO3, 112–117° and 107.4°, respectively.21
formed after the nucleophilic addition of SO3 to the nitrosyl
2−
The bond lengths and angles for the [RuN(O)SO3] moiety of ligand of 2 (eqn (5)). This intense band (ε = 6.0 × 103 M−1
complex 1 are very similar to those reported for cis-[RuCl cm−1) was assigned by TD-DFT as a metal to ligand charge
(bipy)2(N(O)SO3)] (complex 3),1 with differences lower than transfer (MLCT) transition, Ru → N(O)SO3 (inset of Fig. 2B;
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at δ ∼−40.3 ppm25 (Fig. S12 and S13, ESI‡). Correspondingly,
the decomposition of trans-[RuCl(py)4N(O)SO3] in neutral
solution also yields the hydroxo nitrosyl complex
[RuOH(py)4NO]2+.1
In acidic solution (1.0 M trifluoroacetic acid), complex 1
was stoichiometrically converted into the precursor nitrosyl
(complex 2) by heterolytic cleavage of the S–N bond of the N(O)
1
SO3 moiety, based on the FT-IR and H NMR results (Fig. S14
and S15 ESI‡). These findings are in agreement with the data
reported for the complexes cis-[RuCl(bipy)2(N(O)SO3] and
trans-[RuCl(py)4(N(O)SO3)] in aqueous HCl (4.0 M).1
The reaction of hydroxide ions (OH−) with the complexes 1
and 2
One of the main topics of interest in nitrosyl chemistry is
metal nitrosyl complex electrophilicity.1,16a,23,24,26 The reaction
of nitrosyl complexes with a variety of nucleophiles is well
documented, and the main species studied are OH−, HS−, N3
,
−
NH2OH and RS− (thiols). Aiming to investigate the electrophi-
lic character of the N(O)SO3 ligand in 1, the reaction of this
complex and also that of complex 2 with OH− were performed.
Of note, in general, nitrosyl complexes of the type [L5M(NO)]n
react with OH− yielding the respective nitro complexes
[L5M(NO2)](n−2) 16a,24
This reaction was already investigated for
.
a series of trans-[Ru(NH3)4(L)(NO)]3+ nitrosyl complexes,24 but
here we show unprecedented electrophilic behavior of a nitro-
sylsulphito complex.
Fig. 2 (A) Electronic absorption spectra (UV-Vis) of the complexes 1
and 2, both in phosphate buffer pH 7.4. (B) Experimental and theoretical
UV-Vis of 1. Electronic transitions are represented as vertical bars with
height equal to the oscillator strength (f) values. tr. 7, 8 and 10 = elec-
tronic transitions #7, #8 and #10, respectively. Inset: Electron-density
difference maps (EDDM) of the tr. 7, a MLCT Ru → N(O)SO3 (black indi-
cates a decrease in electron density, white indicates an increase; isova-
lue = 0.001).
Both the reactions of 1 and 2 with OH− produced the
respective nitro complex trans-[Ru(NH3)4(isn)(NO2)]+,15,24 with
a characteristic band at λ = 404 nm (Fig. 3). During the reaction
Fig. S6, S7, Table S5, ESI‡). This MLCT transition is of higher
energy in comparison with that of the complexes [Fe(CN)5N(O)
SO3]4–, [RuCl(py)4N(O)SO3] and cis-[RuX(bipy)2N(O)SO3] (X =
Cl− or Br−),1 which are in the range of 450–475 nm.1 The
theoretical spectrum of 1 is in agreement with the experi-
mental results (Fig. 2B and S6 of the ESI‡), and the detailed
assignments of all the electronic absorption bands of 1 are
given in Table S5 (ESI‡).
Thermal stability of 1 at pH 7.4 and under acidic conditions
The thermal stability of 1 was investigated using electronic
absorption (UV-Vis) and 1H NMR spectroscopy (Fig. S8–S11,
ESI‡), and the results showed that 1 is kinetically stable at pH
7.4, with a rate constant of 3.1 × 10−5 s−1 for isn labilization at
298 K (t1/2 ∼ 373 min). The activation parameters for the isn
labilization from 1 are listed in Table S6 (ESI‡). This reaction
is governed by the positive values of the enthalpic (ΔH‡
26.5 kcal mol−1) and entropic terms (ΔS‡ ≈ 9.1 cal mol−1 K−1),
suggesting dissociative (Id) rate-determining step. The
≈
a
product formed after isn labilization from 1 was characterized
by 15N NMR (using 15N-labeled N(O)SO3 ligand in 1) as being
Fig. 3 Representative spectral changes for the reaction of OH− with
the hydroxo nitrosyl complex25 trans-[Ru(NH3)4(OH)(15NO)]2+, the complexes (A) 1 and (B) 2.
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of 1 with OH−, the characteristic band of 1 at 363 nm data on the photochemistry of nitrosylsulphito complexes (to
decreases at the rate that the 404 nm band grows in (Fig. 3A), the best of our knowledge) some comparisons about the
with an isosbestic point at 375 nm. Analogously, the 404 nm photochemistry of 1 will be performed with analogous Ru(II)
band appears as complex 2 reacts with OH−. These results nitro complexes, [L5Ru–NO2]n.
were confirmed by 15N NMR spectroscopy, by means of com-
parisons of the reaction of OH− with 15N-labelled 1 and 2 decreases with the irradiation time of 1 (Fig. S22, ESI‡), and
The MLCT (Ru → N(O)SO3) band at 363 nm (Fig. 2A)
(Fig. S16, ESI‡).15,24 The formation of a single peak at δ15
=
this behavior can be associated with labilization of the N(O)
N
−
158.2 ppm in the 15N NMR (Fig. S16, ESI‡) confirmed that the SO3 ligand. This hypothesis corroborates the results reported
reactions of 1 and 2 with OH− yielded the same product, i.e. for the parent nitro complex trans-[Ru(NH3)4P(OEt)3(NO2)]+
the complex trans-[Ru(NH3)4(isn)(NO2)]+.15,24
(P(OEt)3 = triethyl phosphite),20 and also for other [L5Ru-NO2]n
A complete set of kinetic data for the reaction of OH− with 1 complexes,20,27 which upon irradiation the MLCT band (Ru →
−
and with 2 is provided in the ESI‡ (Fig. S17, S18 and Table S7). NO2) decreases, resulting in labilization of NO2 (eqn (7)) and
Under pseudo-first-order conditions ([OH−] ≫ [complexes 1 no Ru(III) formation:
or 2]) the rate constants for the formation of trans-
hν
n
½L5Ru ꢀ NO2ꢂ ꢀ! ½L5Ru ꢀ ðH2OÞꢂnþþNO2
ð7Þ
ꢀ
[Ru(NH3)4(isn)(NO2)]+ are 2.1 and 10.5 M−1 s−1 (at 288 K) for 1
and 2, respectively (Table S7, ESI‡). The mechanism of the reac-
tion of 1 with OH− was investigated by DFT calculations, and the
results showed that the formation of trans-[Ru(NH3)4(isn)(NO2)]+
occurs by the nucleophilic attack of OH− on the nitrogen atom
of the N(O)SO3 ligand in 1 (Fig. S19 and Table S8, ESI‡). This
finding is in agreement with our experimental results (UV-Vis
and 15N NMR, Fig. 3 and Fig. S16 (ESI‡), respectively) and is
comparable to the mechanism reported for the reaction of OH−
with the family of trans-[Ru(NH3)4(L)(NO)]3+ complexes.15,24
Therefore, the experimental and DFT data showed for the
first time the susceptibility of a nitrosylsulphito ligand to
nucleophilic attack by hydroxide ions, then yielding the
respective Ru(II) nitro complex.
H2O
In some of these nitro complexes, nitric oxide (NO•) was also
detected in solution during photolysis, and this process was
related to secondary photochemical reactions,20,27b eqn (8):
hν
NO2 ꢀ! NO• þ O•ꢀ
ð8Þ
ꢀ
H2O
In analogy to eqn (7) and (8), the products most likely
−
formed upon N(O)SO3 release during irradiation of 1 are the
radical species NO• and SO3•−. To investigate this hypothesis,
catalase was used for the detection of NO•, and DMPO (5,5-
dimethyl-1-pyrroline-N-oxide) for the detection of SO3•−. Of
note, two well-documented procedures used for NO• detection
(oxymyoglobin and PTIO)28 were not effective for distinguish-
ing among the formation of NO• or SO3•− (Fig. S23, S24, ESI‡).
When 1 was irradiated in the presence of catalase two new
bands appeared at 538 and 575 nm (Fig. 4A). This is in agree-
ment with the spectral changes reported for the binding of
NO• to catalase,29 thus confirming the formation of NO•
during irradiation of 1. The EPR results for irradiation of 1 in
pKa of the N(O)SO3 ligand in complex 1
The pKa of the N(O)SO3 ligand was determined spectrophoto-
metrically through titration of 1 with aqueous trifluoroacetic
acid solutions (Fig. S20A, ESI‡). The titration curve is shown in
Fig. S20B (ESI‡), and the pKa values obtained by two treat-
ments (see the Experimental section; Fig. S20B and S21A,
ESI‡) were 5.03 and 5.12, respectively, for the protonation
shown in eqn (6):
trans-½RuðNH3Þ ðisnÞðNðOÞSO3Þꢂþ þ H3Oþ
4
Ð trans-½RuðNH3Þ ðisnÞðNðOÞSO2OHÞꢂ2þ þ H2O ð6Þ
4
Unfortunately, no previous studies on nitrosylsulphito com-
plexes reported pKa values, thus making comparisons not
possible. However, the pKa determined for 1 (eqn (6)) is within
an expected range given that the sulfite ion (SO32−, non-co-
ordinated) has a pKa value of 7.2 (ref. 4c) and that this value
should diminish upon coordination to the nitrosyl precursor
(eqn (5)). From these values, we can estimate that the pKa of
−
the free N(O)SO3 ion (non-coordinated to the Ru complex) is
between 5.1 < pKa < 7.2 (for the protonation of one of the
oxygen atoms of the SO3 moiety).
Fig. 4 Formation of NO• and SO3•− during irradiation of 1. (A) Detection
of NO• by UV-Vis: complex 1 (9.0 mM) + Catalase (∼15 μM) in phosphate
•−
buffer (PBS pH 7.4, 200 mM). (B) Detection of SO3 by EPR (a) EPR:
Photochemistry
complex 1 (0.2 mM) + DMPO (100 mM) irradiated for 1 min (PBS pH 7.4);
−
(b) simulated spectrum: DMPO/•SO3 radical adduct (inset), aN = 14.45
Irradiation of 1 with light of wavelengths of 355 or 410 nm pro-
G and aH = 16.10 G; (c) control: PBS (pH 7.4) + DMPO (100 mM) irra-
diated for 5 min; (d) same solution as in (a) but before irradiation. Both
duces NO•, SO3 and isn in solution, and no Ru(III), as dis-
•−
cussed in detail below. Of note, since there are no available (A) and (B) recorded at T = 25 °C, λirrad = 355 nm.
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Fig. 6 Proposed photochemical mechanism of complex 1. This mecha-
nism is based on detection of the aquo complex trans-[Ru(NH3)4(H2O)
(isn)]2+ by Laser Flash Photolysis (LFP), of nitric oxide (NO•) by the reac-
tion with catalase (by Uv-Vis), of sulfite radical (SO3•−, by EPR using
DMPO as a spin trap), and on DFT results (vide infra).
The DFT analysis of the orbitals involved in this electronic
transition highlights the depopulation of the bonding
HOMO-2 orbital and the population of the antibonding LUMO
as main components, with respect to the Ru–N(O)SO3 bond
(Table S5 and Fig. S7, ESI‡). Geometry optimization shows that
the resulting electronic excited state is significantly distorted
along the z-axis with respect to the GS (labeled S7 in Fig. S25,
ESI‡), with a long Ru–N(O)SO3 bond distance of 2.60 Å (for GS
this bond length is calculated as ∼1.91 Å), thus further sup-
−
porting the mechanism of photolabilization of N(O)SO3 from
Fig. 5 Transient absorption spectra after 355 nm excitation of complex 1.
(A) Transient absorption spectra at different time intervals (11–300 μs);
inset shows the decay profile at λ = 500 nm. (B) Absorption spectrum of
the aquo complex trans-[Ru(NH3)4(H2O)(isn)]2+ and of the transient at
t = 11 μs. Conditions: Phosphate buffer pH 7.4, T = 25 °C.
1 (Fig. 6).
1
Additionally, in situ H NMR of the irradiation of 1 showed
that the isonicotinamide ligand (isn) is also capable of photo-
dissociating from the Ru center (Fig. S26, ESI‡). Since the for-
mation of the aquo complex trans-[Ru(NH3)4(H2O)(isn)]2+ was
identified by LFP (Fig. 5B), the labilization of the isn ligand
the presence of DMPO are depicted in Fig. 4B. The simulated thus must arise from a consecutive photochemical event,
−
spectrum and the hyperfine coupling constants (shown in the occurring after the N(O)SO3 photolabilization, as it is most
caption of Fig. 4) are consistent with those reported for the improbable that irradiation of 1 would cause simultaneous
−
DMPO/•SO3− adduct,3d,30 thus confirming SO3•− as a photopro- labilization of both N(O)SO3 and isn ligands. Analogous con-
duct of 1 (Fig. 4B). Therefore, the hypothesis that irradiation of secutive dual photolyses have been previously reported for
1 could result in the formation of NO• and SO3 species was other Ru(II) systems, in which two ligands were photolabilized
•−
confirmed.
during irradiation.32 Moreover, the band at 480 nm observed
Transient absorption Laser Flash Photolysis (LFP) studies in the transient spectra (by LFP) is formed and then decays
were performed to gain further insight into the photochemis- (Fig. 5A), showing that the isn labilization occurs after dis-
−
try of 1. The transient spectra obtained after laser excitation of sociation of N(O)SO3 from 1. This conclusion is based on the
1 are shown in Fig. 5A. The transient spectrum has a fact that the 480 nm band is a MLCT Ru → isn transition31 of
maximum at 480 nm (Fig. 5A), and as can be seen in Fig. 5B, the aquo complex trans-[Ru(NH3)4(H2O)(isn)]2+, and the decay
this band matches the band of the aquo complex trans- of this band would be related to the labilization of the isn
[Ru(NH3)4(H2O)(isn)]2+ at λmax = 480 nm(ref. 31) (in this aquo ligand, in agreement with the 1H NMR results of the in situ
complex the coordinated H2O has a pKa value of 11.731a). irradiation of 1.
Therefore, the transient spectrum (Fig. 5) can be assigned to
the photoproduct aquo complex trans-[Ru(NH3)4(H2O)(isn)]2+, when LFP experiments with complex 1 were performed in the
formed upon irradiation of 1. presence of an excess of DMPO or of isonicotinamide. This
Identical results to those shown in Fig. 5 were obtained
LFP thus supports the hypothesis that the N(O)SO3 ligand result shows that the formation of the aquo complex trans-
dissociates from the Ru center upon irradiation of 1, forming [Ru(NH3)4(H2O)(isn)]2+, followed by its decay (Fig. 5), is not
the aquo complex and the radical species NO• and SO3•−, as directly influenced by the presence or absence of either the
summarized in Fig. 6. This mechanism is also supported by sulfite radical (SO3•−) or the isn ligand in solution.
DFT calculations on the electronic excited state resulting from
In addition, the quantum yield (ϕ) for the photoinduced
excitation of the MLCT Ru → N(O)SO3 of 1 (tr. 7 in Fig. 2B). labilization of the ligands in complex 1 was measured using
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electronic absorption spectroscopy by monitoring the decrease
of its MLCT band (363 nm) during 355 nm irradiation
(Fig. S22, ESI‡), and was calculated as ϕ = 0.12 0.03. Very
similar ϕ values were obtained by monitoring the photodisso-
ciation of isn by 1H NMR for the in situ irradiation of 1
(Fig. S26, ESI‡).
In summary, light irradiation of 1 leads to the labilization
of N(O)SO3−, which then undergoes rapid homolysis to form
NO• and SO3 (Fig. 6). Therefore, the two possible pathways
•−
•−
for the formation of NO• and SO3 are through thermal and
−
photochemical decomposition of the free N(O)SO3 ion: (i) by
−
the thermal homolysis of the S–N bond of the N(O)SO3 ion,
•−
thus dissociating into NO• and SO3 radicals and (ii) by the
−
photodecomposition of N(O)SO3 through a process similar to
Fig. 7 Reaction coordinate of the thermal decomposition of the S–N
that observed during photolysis of S-nitrosothiols (via for-
mation of NO• and thiyl radicals,33 and also analogous to the
mechanism observed for the photodecomposition of the nitro
ligand in Ru(II) nitro complexes,20 eqn (7) and (8)).
−
bond of the ion N(O)SO3 (left). Transition state (middle), and NO• and
SO3•− (right).
(ΔG‡ = 13 kcal mol−1, Fig. 7), this reaction is nearly instan-
taneous at room temperature (298 K). This is in agreement
with the above results (Fig. 4) which demonstrated that the
Molecules with S–N bonds and structures similar to N(O)
SO3−, such as thionitrous acid (HSNO, S–N bond length of
1.78–1.93 Å)34 and other S-nitrosothiols, are proposed to
undergo light induced homolysis of the weak S–N bond.33
Therefore, the two possible pathways for N(O)SO3 decompo-
sition, i.e. (i) thermal and (ii) photochemical S–N cleavage, are
radicals NO• and SO3 are formed upon irradiation of 1, thus
•−
−
corroborating with the mechanism proposed (Fig. 6).
The enthalpy of the reaction in eqn (9) at 298 K (ΔrH298),
which is by definition35 the bond dissociation enthalpy (BDE)
of the ion N(O)SO3−, was calculated according to the litera-
ture.36 The BDE of this reaction (eqn (9)) was predicted as
both likely to occur. The investigation of the mechanism for
the formation of NO• and SO3 radicals from N(O)SO3 was
performed by DFT, and the results are provided in detail in the
next section.
•−
−
17.8 kcal mol−1
.
Formation of NO• and SO3•− by the S–N bond dissociation of
N(O)SO3
ꢀ
•ꢀ
NðOÞSO3 ! NO• þ SO3
ð9Þ
−
As discussed in the crystallographic section, the S–N bond
length of the N(O)SO3 ligand in 1 is 1.84 Å, ca. 10% longer
The S–N BDE of N(O)SO3− is smaller than that predicted for
a series of representative S-nitrosothiols (CH3SNO,
−
than that of other S–N compounds. Therefore, it is not surpris- CH3CH2SNO, (CH3)2CHSNO (CH3)3CSNO, CH2CHSNO, ca.
ing that the N(O)SO3 anion (formed in solution after 23.3–32.4 kcal mol−1),37 and this can be explained by the fact
−
irradiation of 1) may rapidly decompose to form NO• and that SO3•− is a resonance-stabilized radical. Indeed, this behav-
SO3•− (Fig. 6), and this event is likely to occur through thermal ior was already observed in that series of S-nitrosothiols, in
and photochemical reaction pathways.
which the vinyl-substituted thiol (CH2CHSNO) had the smal-
Unconstrained geometry optimizations of N(O)SO3 were lest BDE of the series (23.3 kcal mol−1) because of the reso-
performed on both the singlet and triplet surfaces. The result- nance-stabilized thiyl radical formed after the homolytic S–N
ing singlet structure is 10.7 kcal mol−1 more stable than the dissociation (the BDE values of the other S-nitrosothiols of the
−
−
optimized triplet structure (thus showing that N(O)SO3 has a series were in the range of 31.3–32.4 kcal mol−1).37
singlet ground state), and has a 1.877 Å S–N bond length. The
The second pathway investigated by DFT for the dis-
−
•−
energy profile of the thermal homolysis of the S–N bond of sociation of the N(O)SO3 into NO• and SO3 radicals is the
−
N(O)SO3 (singlet) is shown in Fig. 7. The transition state for photochemical. The theoretical UV-Vis absorption spectrum of
homolysis has ΔG‡ = 13 kcal mol−1, a single normal mode N(O)SO3 is characterized by a series of transitions in the UV
−
with a low imaginary frequency of −40.85 cm−1 (due to the region, plus a transition in the far red-region (Fig. 8A). Among
large reduced masses of the NO and SO3 fragments, Fig. S28, the seven electronic transitions (tr.1–tr.7, Fig. 8A), tr.1 and
ESI‡), and a bond length of 2.451 Å. Collectively, these geo- tr.2 have the smallest oscillator strengths. The first six elec-
metric and electronic structure parameters indicate that the tronic transitions (tr.1–tr.6 in Fig. 8A) all involve the popu-
transition state is late on the homolysis pathway, and proceeds lation of the LUMO, that is antibonding along the S–N bond
after substantial S–N bond cleavage has occurred. The NO• and (Table S9, ESI‡). In particular, the first electronic excited state
SO3•− products collectively have ΔG = 6.4 kcal mol−1 above that (S1) has strong dissociative nature. This can be clearly seen by
of the N(O)SO3− molecule (Fig. 7), showing that S–N homolysis the related electron density difference map (Fig. 8B) that
is slightly endergonic. According to the energy barrier pre- shows a loss of electron density along the S–N bond (black
−
dicted for the thermal homolysis of the S–N bond of N(O)SO3
surface), as a consequence of the electronic transition (tr. 1).
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−
SO3 (Fig. 6), which then dissociates by the thermolysis of the
S–N bond (Fig. 7), yielding NO• and SO3
.
•−
Conclusion
−
In summary, the stabilization of N(O)SO3 provided by its
coordination in complex 1 allowed us to better understand the
chemical properties of this anion. Our study on the stability of
1 at neutral and acidic pH is in accordance with previous
studies of nitrosylsulphito complexes. The electrophilic behav-
−
ior described here for N(O)SO3 in 1 is the first reported for
nitrosylsulphito complexes, and we furthermore showed that
the nucleophilic attack of OH− on 1 produces the respective
Ru(II) nitro complex. Therefore, these results provide a useful
−
insight to understand the reaction pathways of N(O)SO3
under biological conditions, where hydrolysis and attack by
nucleophilic species are speculated. Also, the photochemical
results presented here are the first described for the nitrosyl-
sulphito complexes, and demonstrated the production of two
important radicals, NO• and SO3•−, when 1 was irradiated with
light. In the context of applications, the main advantage of
triggering the release of NO• and SO3 by light is the possi-
•−
Fig. 8 (A) Theoretical electronic absorption spectrum (UV-Vis) of N(O)
SO3−. Electronic transitions are represented as vertical bars with height
bility of control of dosage and timing (i.e. on demand release).
Hence, the results showed that complex 1 has significant
−
equal to the oscillator strength (f) values. Inset: Structure of N(O)SO3
.
potential as a photoactive source of the radical species NO•
(B) Electron-density difference maps (EDDM) (black indicates a decrease
in electron density, white indicates an increase; isovalue = 0.001) and
•−
and SO3
.
main component orbitals (HOMO and LUMO) of the 1st singlet–singlet
Based on the importance and applications of both nitric
−
transition (tr. 1) computed for N(O)SO3
.
•−
oxide and SOx radicals (eqn (1)–(4)), the studies performed
here with complex 1 contribute to the development of other
stable and water-soluble [L5M–N(O)SO3]n complexes tuned to
•−
release NO• and SO3 over an expanded range of wavelengths,
The geometry optimization of the first singlet excited state (S1)
further supports its dissociative nature. The relaxed geometry
displays a S–N bond length of 2.20 Å, about 0.25 Å longer with
respect to the ground state (Fig. S29, ESI‡). Although S1 can be
hardly populated directly by light absorption due to the extre-
mely low value of the oscillator strength of the tr.1, Fig. 8A
(which is also low for tr.2 and tr.3), it can be assumed that S1
is the arrival point of the de-excitation process from higher
mainly for biological purposes.
Experimental
Chemicals
Unless otherwise noted, reagents and solvents were purchased
from Sigma-Aldrich, Merck or JT Baker at the highest quality
available and were used without further purification. Milli-Q
water (18.2 MΩ) was used throughout the experiments.
Ruthenium(III) chloride hydrate (Strem Chemicals) was the syn-
thetic precursor of all the ruthenium complexes. Sodium
sulfite anhydrous (Na2SO3, Merck) was used for the synthesis
of the nitrosylsulphito complexes. Unless otherwise noted, all
solutions were deaerated with Ar (99.999%) for at least 30 min.
−
electronic excited states. Therefore, irradiation of N(O)SO3
with light might lead to the formation of NO• and SO3•−, but
this process seems to be favorable only for irradiation with UV
light of higher energy (i.e. λirrad < 300 nm), in which the oscil-
lator strengths have higher values (Fig. 8A). However, λirrad
<
300 nm is out of the range used in this study.
Overall, our data support the view that the decomposition
of N(O)SO3 into NO• and SO3 (eqn (9)) could occur by both
thermal and photochemical pathways. Nevertheless, because
−
•−
−
General
of the very low oscillator strengths predicted for N(O)SO3 in
the wavelength range of 300–900 nm (Fig. 8A), the thermal Electronic spectra (UV-Vis) were recorded on a Shimadzu
pathway is favored regarding the photochemical one. UV3600 or in a Thermo Scientific Multiskan GO UV-Vis
Moreover, based on the low energy barrier predicted for the spectrophotometer, using a 1.00 cm quartz cell. Infrared
thermal homolysis of the S–N bond (∼13 kcal mol−1, Fig. 7), spectra were recorded in a Shimadzu FTIR Spectrophotometer
−
the dissociation of N(O)SO3 (eqn (9)) should occur instan- model IRAffinity-1 (for KBr pellets experiments), or in a Vertex
taneously at room temperature. Therefore, the irradiation of 70v Bruker (for the experiments in solution). 1H- and 15N-NMR
complex 1 with light leads to the photodissociation of N(O) spectra were recorded on an Agilent 500 MHz NMR
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Spectrometer
(Model
500/54
Premium
Shield).
3- The model was refined by full-matrix least squares on F2 by
(Trimethylsilyl)propionic-2,2,3,3-d4 (TMSP-d4) was used as an means of SHELXL-97.41 All hydrogen atoms were stereochemi-
1
internal reference (δ = 0 ppm) for H NMR experiments, and a cally positioned and refined with the ridging model. Fig. 1 and
glass capillary filled with 15NH4Cl (δ = –354 ppm vs. chemical S30 (ESI‡) were prepared using Mercury 3.9.39 Structure solu-
shift of CH3NO2, δCH NO = 0 ppm) was used as reference in the tion, refinement and hardware details are in the corres-
3
2
15N-NMR experiments. Electron paramagnetic resonance (EPR) ponding cif file. Listing of atomic coordinates and equivalent
spectra were recorded in a Bruker EMX Plus X-band spectro- isotropic displacement parameters, full intramolecular bond
meter at room or liquid nitrogen temperature (77 K). distances and angles, hydrogen coordinates, and anisotropic
Elemental analysis was performed in a PerkinElmer 2400 thermal parameters of complex 2 are available from the
Series II CHNS/O Elemental Analyzer.
authors and were deposited at the Cambridge Crystallographic
Data Centre, reference number CCDC 1922883.†
pKa of the N(O)SO3 ligand in complex 1. An aqueous solu-
Synthesis
The synthetic precursor complexes15,22,38 [RuCl(NH3)5]Cl3, tion (20.0 mL) with pH 7.9 and I = 0.1 M (CF3COONa) contain-
trans-[RuCl(NH3)4(SO2)]Cl, trans-[Ru(SO4)(NH3)4(isn)]Cl (isn = ing the complex trans-[Ru(NH3)4(isn)(N(O)SO3)]+ (C = 1.8 × 10−4
isonicotinamide), trans-[Ru(NH3)4(isn)(NO)](BF4)3, and the M) was titrated with small volumes (2.0–5.0 μL) of trifluoroace-
aquo complex31 trans-[Ru(NH3)4(H2O)(isn)](PF6)2 were pre- tic acid (HTFA) with a molarity of 0.01 to 1.0 M, and the pro-
pared and characterized as described elsewhere.15,22,31,38 The gress was monitored by the decrease of the band at 363 nm by
15N-labeled trans-[Ru(NH3)4(isn)(15NO)](BF4)3 was synthesized UV-Vis. The pKa was determined by spectrophotometry42
using Na15NO2.28c
through a graphical solution of eqn (10), where A = observed
Complex 1, trans-[Ru(NH3)4(isn)(N(O)SO3)](PF6). 25 mg of absorbance (absorbance of the mixture A = AI + AM), where
complex 2 (4.3 × 10−5 mol) was added to 1.5 mL of argon AM = absorbance of the molecular species, and AI = absorbance
degassed water at T = 25 °C, followed by the addition of 9 mg of the ionized species.
of sodium sulfite (Na2SO3, 7.1 × 10−5 mol) under vigorous stir-
pH ¼ pKa þ log ½ðA ꢀ AMÞ=ðAI ꢀ AÞꢂ
ð10Þ
ring. After 1 min, 150 mg of NH4PF6 (9.2 × 10−4 mol) was
added, resulting in the precipitation of crystals of the nitrosyl-
sulphito complex after 30–60 min upon cooling on an ice-bath
pKa was also determined by the first and second derivative
of the titration curve.
or
a refrigerator. Yield = 60–65%. Elemental Analysis
(C6H18F6N7O5PRuS) – Theoretical: C = 13.19%; H = 3.32%; N =
17.95%; S = 5.87%. Experimental: C = 13.60%; H = 3.39%; N =
17.79%; S = 5.69%.
Stability of complex 1 in aqueous solutions
pH 7.4. Stability assays of complex 1 were performed under
phosphate buffer pH 7.4, C = 20 mM, I = 0.22 M CF3COONa.
The reaction course was followed by electronic spectroscopy
(UV-Vis) at different temperatures; using the Arrhenius
Equation and Eyring plots, the activation parameters, acti-
vation energy (Ea), enthalpy (ΔH‡), entropy (ΔS‡) of activation
and Gibbs energy of activation (ΔG‡), were calculated. The
reaction course was also monitored by 1H-, and 15N-NMR
using the 15N-labeled complex 1.
trans-[Ru(NH3)4(isn)(15N(O)SO3)](PF6).
The
15N-labeled
complex trans-[Ru(NH3)4(isn)(15N(O)SO3)](PF6) (15N-labeled
complex 1) was prepared following the same methodology
described above, but using the 15N-labeled precursor trans-[Ru
(NH3)4(isn)(15NO)](BF4)3.28c
X-ray data collection and structure determination
Complex 1, trans-[Ru(NH3)4(isn)(N(O)SO3)](PF6). A green
crystal of dimensions 0.1 × 0.1 × 0.3 mm3 was selected and
mounted on an XtaLAB Mini Rigaku diffractometer. Data were
collected at room temperature up to 52° in 2θ; final unit cell
parameters were based on all reflections. Multi-scan absorp-
tion corrections were applied. Structure solution, refinement
and hardware details are in the corresponding cif file. Listing
of atomic coordinates and equivalent isotropic displacement
parameters, full intramolecular bond distances and angles,
hydrogen coordinates, and anisotropic thermal parameters are
available from the authors and were deposited with the
Cambridge Crystallographic Data Centre, reference number
1915847. Fig. 1 and Fig. S4 (ESI‡) were prepared using the soft-
1.0 M of trifluoroacetic acid (HTFA). Complex 1 was solu-
bilized in a solution of deuterated trifluoroacetic acid (DTFA,
1.0 M), and the product was characterized by 1H NMR. This
1
result was compared to the H-NMR spectrum of a solution of
the nitrosyl complex 2 under the same conditions (1.0 M
DTFA). FT-IR assays (in solution) were also performed for 1 in
1.0 M HTFA (trifluoroacetic acid), and in aqueous solution
(control). The FT-IR spectrum of the nitrosyl complex (complex
2) under the same conditions (1.0 M HTFA) was also recorded
for comparisons.
Reaction of hydroxide ions (OH−) with complexes 1 and 2
ware Mercury 3.9.39 Crystal data and structure refinement, The reaction of complexes 1 and 2 with hydroxide ions (OH−)
listing of atomic coordinates and equivalent isotropic displace- was performed using the same methodology described for the
ment parameters, and full intramolecular bond distances and reaction of a series of nitrosyl complexes with OH−,24 which is
angles are provided in Tables S1–S3 (ESI‡).
briefly described below. The reaction progress was followed by
Complex 2, trans-[Ru(NH3)4(isn)(NO)](BF4)3. The structure electronic spectroscopy (UV-Vis), under pseudo-first order con-
of complex 2 was solved by direct methods with SHELXS-97.40 ditions ([OH−] ≫ [Ru]). Aqueous solutions of the Ru complexes
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(CRu = 1.0 × 10−4 M) and OH− ranging from 0.01 M to 0.045 M, France) attenuated to 15 mJ cm−2 as the excitation source with
with ionic strength I = 1.0 M (NaCl), and in the temperature 8 ns of pulse duration. The signal from the photomultiplier
ranges T = 15 and 25 °C (for 1) and 15 °C for 2, were used. At detection system was captured by using a Tektronix TDS 2012
least five experiments were performed for each concentration digitizer (Beaverton, OR, USA). The FFP-112 ns and the digitizer
of OH− used. This afforded at least 25 values for the observed were connected to a personal computer via General Purpose
rate constant (kobs). Plots of kobs versus [OH−] were built for Instrumentation Bus (GPIB) and serial interfaces controlling all
both complexes. In all cases, a linear distribution was the experimental parameters and providing suitable processing
observed. The slope was equal to the second-order rate con- and data storage capabilities using a proprietary software
stant. 15N-NMR spectra were also recorded for the reaction of package developed in a LabView environment and compiled as
OH− with the 15N-labeled complexes 1 and 2 in order to a stand-alone application (Luzchem, Ottawa, Canada). Each
characterize the products formed.
kinetic trace was averaged 16 times, and observed rate constants
Photochemical experiments. The UV light source was a Nd: were determined by parameter fitting to exponential decay func-
YAG laser (Continuum, model Serulite-II) operating in the tions. All measurements were performed with aqueous phos-
third harmonic (λ = 355 nm). The pulse energy was measured phate buffer solutions pH 7.4 (20 mM, I = 0.22 M), thermo-
by using a power meter (Coherent, Lasermate-P) and was statted at 25.0 0.5 °C, and purged with high-purity Argon for
adjusted to ∼5 mJ per pulse; the pulse frequency was 10 pulses at least 30 min before the experiments. Samples were held
per s. Spectral changes during photolysis were measured by under Argon in a round bottom flask, connected to a quartz
electronic spectroscopy (UV-Vis). The visible light source was a flux cuvette by Tygon tubing, and pumped into the cuvette at a
SD Laser 303, λ = 410 5 nm, output power = 5 mW. For the flow rate of about 0.5 mL min−1
photolysis followed by 1H-NMR, solutions were placed in the
Density functional theory (DFT). All the calculations were
.
NMR tube and irradiated in situ (with 410 nm light), or ex situ performed by using the Gaussian 09 Revision C.01 (G09)
(with 355 nm light). For the EPR assays (detection of Ru(III)), program package,43 employing density functional theory (DFT)
solutions were irradiated in a cuvette at room temperature and and time dependent (TD)-DFT methods.44 Calculations were
then rapidly transferred to EPR tubes and frozen to N2 liquid run using the Becke three-parameter hybrid functional,45 and
temperature (77 K) to record the spectra.
the Lee–Yang–Parr gradient-corrected correlation functional
For the detection of the sulfite radical species (SO3•−) by (B3LYP).46 The solvent effect was included using the polariz-
EPR spectroscopy, irradiation of 1 was performed in situ able continuum model (PCM) with water as the solvent.47 The
(quartz capilar), and the detection was accomplished using the SDD basis set48 and effective core potential were used for the
spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The EPR Ru atom. The 6-31G** basis set49 was used for all the other
−
spectra were recorded at room temperature (T = 25 °C), and the atoms, while the photochemistry of N(O)SO3 was treated at
spectrometer settings were as follows: modulation frequency, the 6-311++G** level. The complete reaction profile has been
100 kHz; modulation amplitude, 1.0 G; microwave power, studied for the addition of OH− to 1 (B3LYP/SDD/6-31G**
2 mW; microwave frequency, 9.79 GHz; field sweep, 100 G; level). Geometry optimizations were carried out without any
receiver gain, 5 × 104; time constant, 20.48 ms; sweep time, symmetry constraints. The nature of the stationary points in
41.94 s; number of scans, 1. Computer simulations of the EPR the potential energy hypersurface was characterized either as
spectra were performed using SimFonia software.
minima or transition states by using harmonic vibrational fre-
In the experiments using catalase (from bovine liver, quency calculations. No imaginary frequencies were found for
2000–5000 units per mg protein, Sigma) for the detection of minima, thus indicating that we had located the minima on
nitric oxide (NO•), fresh stock solutions of catalase were pre- the potential-energy surfaces, while a single imaginary fre-
pared in phosphate buffer pH 7.4, diluted to reach the desired quency was found for transition states. UV-Vis electronic
concentration (λmax = 403 nm, ε = 4.3 × 105 M−1 cm−1 29
)
and the absorption spectra of 1 and of N(O)SO3 in the GS were simu-
−
photolysis was performed in a cuvette at T = 25 °C; the spectral lated by using TD-DFT, computing a total of 80 and 16 singlet
changes were monitored by electronic spectroscopy (UV-Vis). excited states, respectively. The electronic distribution and the
Experiments using oxymyoglobin (oxyMb)28b,c and carboxy- localization of the singlet excited states were visualized by
PTIO28a for the detection of NO• followed previously published using electron-density difference maps (EDDMs). GaussSum
procedures.28a,b,c Phosphate buffer solutions (pH 7.4) contain- 2.2.550 was used to simulate the theoretical UV-Vis spectra and
ing sodium sulfite (Na2SO3) and PTIO or oxyMB were photo- for the extraction of EDDMs.51 Molecular-graphic images were
lyzed in a 1.00 path quartz cuvette; in the case of oxyMb, the produced by using the UCSF Chimera package from the
reaction course was followed by UV-Vis spectroscopy, and in Resource for Biocomputing, Visualization, and Informatics at
the case of PTIO, by EPR spectroscopy.
the University of California, San Francisco.52 For the thermal
In all cases, the experimental details, such as concentration dissociation of N(O)SO3−, the reaction coordinate structures
and temperature used, are described in the caption of the figures. were calculated with the basis set qzvp, the functional B3LYP
Laser flash photolysis (LFP). LFP experiments were per- within the spin unrestricted formalism, and a water solvent
formed in a LFP-112 ns laser flash photolysis spectrometer (PCM). Transition state calculations were performed with the
(Luzchem Ottawa, Canada) using the third harmonic (355 nm) O–N–S–O dihedral frozen at 0 degrees from the eclipsed
of a pulsed QSwitched Nd:YAG laser (Brilliant-B, LesUlis, configuration.
Dalton Trans.
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10 M. Roginskaya, R. Mohseni, D. Ampadu-Boateng and
Y. Razskazovskiy, Free Radical Res., 2016, 50, 756–766.
11 (a) C. B. Bai, N. X. Wang, X. W. Lan, Y. J. Wang, Y. L. Xing,
J. L. Wen, X. W. Gao and W. Zhang, Sci. Rep., 2016, 6,
20163; (b) Y. F. Guo, S. Mahmood, B. H. Xu, X. Q. Yao,
H. Y. He and S. J. Zhang, J. Org. Chem., 2017, 82, 1591–
1599.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
The authors are grateful for the financial support by the 12 (a) S. N. Mendiara, E. Ghibaudi, L. J. Perissinotti and
Brazilian agencies FAPESP (12/23651-4, 17/01189-0) and CNPq
(306491/2015-0). This study was financed in part by the
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior -
A. J. Colussi, J. Phys. Chem., 1992, 96, 8089–8091;
(b) S. B. Oblath, S. S. Markowitz, T. Novakov and
S. G. Chang, J. Phys. Chem., 1982, 86, 4853–4857.
Brasil (CAPES) - Finance Code 001. Dr. Gustavo Metzker is 13 J. H. Swinehart, Coord. Chem. Rev., 1967, 2, 385–402.
acknowledged for the critical review of this manuscript and 14 (a) W. Moser, R. A. Chalmers and A. G. Fogg, J. Inorg. Nucl.
Dr. Elena Amadio for help in the realization of the cover artwork.
Chem., 1965, 27, 831–840; (b) A. G. Fogg, A. H. Norbury and
W. Moser, J. Inorg. Nucl. Chem., 1966, 28, 2753–2755.
15 E. Tfouni, M. Krieger, B. R. McGarvey and D. W. Franco,
Coord. Chem. Rev., 2003, 236, 57–69.
Notes and references
16 (a) M. L. Souza, A. C. Roveda Jr., J. C. M. Pereira and
D. W. Franco, Coord. Chem. Rev., 2016, 306, 615–627;
(b) Y. Gao, A. Toubaei, X. Q. Kong and G. Wu, Chem. – Eur.
J., 2015, 21, 17172–17177; (c) M. M. Cortese-Krott,
A. R. Butler, J. D. Woollins and M. Feelisch, Dalton Trans.,
2016, 45, 5908–5919; (d) M. A. Rhine, B. C. Sanders,
A. K. Patra and T. C. Harrop, Inorg. Chem., 2015, 54, 9351–
9366; (e) Y. Gao, B. Mossing and G. Wu, Dalton Trans.,
2015, 44, 20338–20343; (f) J. C. M. Pereira, M. L. Souza and
D. W. Franco, Eur. J. Inorg. Chem., 2015, 2015, 1005–1011;
(g) L. L. Perissinotti, D. A. Estrin, G. Leitus and
F. Doctorovich, J. Am. Chem. Soc., 2006, 128, 2512–2513;
(h) L. L. Perissinotti, G. Leitus, L. Shimon, D. Estrin and
F. Doctorovich, Inorg. Chem., 2008, 47, 4723–4733;
(i) F. Roncaroli and J. A. Olabe, Inorg. Chem., 2005, 44,
4719–4727; ( j) M. R. Filipovic, M. Eberhardt, V. Prokopovic,
A. Mijuskovic, Z. Orescanin-Dusic, P. Reeh and I. Ivanovic-
Burmazovic, J. Med. Chem., 2013, 56, 1499–1508;
(k) S. L. Quiroga, A. E. Almaraz, V. T. Amorebieta,
L. L. Perissinotti and J. A. Olabe, Chem. – Eur. J., 2011, 17,
4145–4156.
1 F. Bottomley, W. V. F. Brooks, D. E. Paez, P. S. White and
M. Mukaida, J. Chem. Soc., Dalton Trans, 1983, 2465–2472.
2 (a) U. Takahama and S. Hirota, J. Agric. Food Chem., 2012,
60, 1102–1112; (b) H. Vally, N. L. A. Misso and V. Madan,
Clin. Exp. Allergy, 2009, 39, 1643–1651.
3 (a) P. B. Woolsey, J. Altern. Complement. Med., 2008, 14,
1159–1164; (b) C. Mottley, R. P. Mason, C. F. Chignell,
K. Sivarajah and T. E. Eling, J. Biol. Chem., 1982, 257, 5050–
5055; (c) K. Ranguelova, S. Chatterjee, M. Ehrenshaft,
D. C. Ramirez, F. A. Summers, M. B. Kadiiska and
R. P. Mason, J. Biol. Chem., 2010, 285, 24195–24205;
(d) K. Ranguelova, A. B. Rice, A. Khajo, M. Triquigneaux,
S. Garantziotis, R. S. Magliozzo and R. P. Mason, Free
Radical Biol. Med., 2012, 52, 1264–1271; (e) K. Ranguelova,
A. B. Rice, O. M. Lardinois, M. Triquigneaux,
N. Steinckwich, L. J. Deterding, S. Garantziotis and
R. P. Mason, Free Radical Biol. Med., 2013, 60, 98–106;
(f) M. Velayutham, C. F. Hemann, A. J. Cardounel and
J. L. Zweier, Biochem. Biophys. Rep., 2016, 5, 96–104;
(g) W. T. Lee, Brain Dev., 2011, 33, 745–752.
4 (a) H. J. Cohen and I. Fridovich, J. Biol. Chem., 1971, 246, 17 T. Chivers and R. S. Laitinen, Chem. Soc. Rev., 2017, 46,
359–366; (b) J. L. Johnson and K. V. Rajagopalan, J. Biol. 5182–5192.
Chem., 1977, 252, 2017–2025; (c) K. Ranguelova and 18 (a) W. Deng, H. L. Zhao, F. P. Pan, X. H. Feng, B. Jung,
R. P. Mason, Free Radical Biol. Med., 2009, 47, 128–134.
5 (a) E. Hayon, A. Treinin and J. Wilf, J. Am. Chem. Soc., 1972,
94, 47–57; (b) P. Neta, R. E. Huie and A. B. Ross, J. Phys.
Chem. Ref. Data, 1988, 17, 1027–1284.
6 R. E. Huie and P. Neta, J. Phys. Chem., 1984, 88, 5665–5669.
7 L. Eberson, Adv. Phys. Org. Chem., 1982, 18, 79–185.
8 Y. Guo, X. Lou, C. Fang, D. Xiao, Z. Wang and J. Liu,
Environ. Sci. Technol., 2013, 47, 11174–11181.
A. Abdel-Wahab, B. Batchelor and Y. Li, Environ. Sci.
Technol., 2017, 51, 13372–13379; (b) A. Fraix and S. Sortino,
Photochem. Photobiol. Sci., 2018, 17, 1709–1727; (c) R. Radi,
Proc. Natl. Acad. Sci. U. S. A., 2018, 115, 5839–5848;
(d) S. Sortino, Chem. Soc. Rev., 2010, 39, 2903–2913;
(e) L. Chen, M. Tang, C. Chen, M. Chen, K. Luo, J. Xu,
D. Zhou and F. Wu, Environ. Sci. Technol., 2017, 51, 12663–
12671; (f) D. N. Zhou, L. Chen, J. J. Li and F. Wu, Chem.
Eng. J., 2018, 346, 726–738.
9 (a) Y. Deng and C. M. Ezyske, Water Res., 2011, 45, 6189–
6194; (b) D. N. Zhou, H. Zhang and L. Chen, J. Chem. 19 D. M. P. Mingos, Nitrosyl Complexes in Inorganic Chemistry,
Technol. Biotechnol., 2015, 90, 775–779; (c) Y. Yang, J. Jiang,
X. L. Lu, J. Ma and Y. Z. Liu, Environ. Sci. Technol., 2015, 49,
Biochemistry and Medicine I, Springer, Heidelberg,
New York, Dordrecht, London, 2014.
7330–7339; (d) L. S. Lian, B. Yao, S. D. Hou, J. Y. Fang, 20 R. M. Carlos, D. R. Cardoso, E. E. Castellano, R. Z. Osti,
S. W. Yan and W. H. Song, Environ. Sci. Technol., 2017, 51,
2954–2962.
A. J. Camargo, L. G. Macedo and D. W. Franco, J. Am.
Chem. Soc., 2004, 126, 2546–2555.
This journal is © The Royal Society of Chemistry 2019
Dalton Trans.

View Article Online
Paper
Dalton Transactions
21 A. F. Holleman and E. Wiberg, Inorganic Chemistry, Academic 38 M. G. Gomes, C. U. Davanzo, S. C. Silva, L. G. F. Lopes,
Press, San Diego; De Gruyter, Berlin, New York, 2001.
22 S. S. Borges, C. U. Davanzo, E. E. Castellano, J. Z-Schpector,
P. S. Santos and D. W. Franco, J. Chem. Soc., Dalton Trans,
1998, 601–607.
S. C. Silva and D. W. Franco, Inorg. Chem., 1998, 37, 2670– 39 C. F. Macrae, P. R. Edgington, P. McCabe, E. Pidcock,
2677.
G. P. Shields, R. Taylor, M. Towler and J. van De Streek,
J. Appl. Crystallogr., 2006, 39, 453–457.
40 G. M. Sheldrick, SHELXS97 Program for Crystal Structure
Refinement, University of Gottingen, Gottingen, Germany,
1997.
23 F. Doctorovich and F. Di Salvo, Acc. Chem. Res., 2007, 40,
985–993.
24 F. Roncaroli, M. E. Ruggiero, D. W. Franco, G. L. Estiu and
J. A. Olabe, Inorg. Chem., 2002, 41, 5760–5769.
25 M. A. Il’yin, V. A. Emel’anov, A. V. Belyaev, A. N. Makhinya, 41 G. M. Sheldrick, SHELXS97, Program for Crystal Structure
S. V. Tkachev and N. I. Alferova, Russ. J. Inorg. Chem., 2008,
53, 1070–1076.
Analysis, University of Gottingen, Gottingen, Germany,
1997.
26 F. Bottomley, Acc. Chem. Res., 1978, 11, 158–163.
27 (a) C. A. Bignozzi, C. Chiorboli, Z. Murtaza, W. E. Jones
and T. J. Meyer, Inorg. Chem., 1993, 32, 1036–1038;
42 A. Albert and E. P. Serjeant, The Determination of Ionization
Constants:
A Laboratory Manual, Chapman and Hall,
New York, 1984.
(b) R. G. Lima, M. G. Sauaia, D. Bonaventura, 43 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
A. C. Tedesco, R. F. V. Lopez, L. M. Bendhack and R. S. da
Silva, Inorg. Chim. Acta, 2005, 358, 2643–2650.
M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone,
B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato,
X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng,
J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda,
J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao,
H. Nakai, T. Vreven, J. A. Montgomery Jr., J. E. Peralta,
F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers,
K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand,
K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar,
J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene,
J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo,
R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin,
R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin,
K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador,
J. J. Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas,
J. B. Foresman, J. V. Ortiz, J. Cioslowski and D. J. Fox,
Gaussian 09, Gaussian, Inc., Wallingford CT, 2009.
28 (a) A. C. Roveda Jr., T. B. R. Papa, E. E. Castellano and
D. W. Franco, Inorg. Chim. Acta, 2014, 409 part A, 147–155;
(b) A. C. Merkle, A. B. McQuarters and N. Lehnert, Dalton
Trans., 2012, 41, 8047–8059; (c) A. C. Roveda Jr.,
H. D. Aguiar, K. M. Miranda, C. C. Tadini and
D. W. Franco, J. Mater. Chem. B, 2014, 2, 7232–7242.
29 M. Hoshino, K. Ozawa, H. Seki and P. C. Ford, J. Am. Chem.
Soc., 1993, 115, 9568–9575.
30 G. R. Buettner, Free Radical Biol. Med., 1987, 3, 259–303.
31 (a) C. C. Kuehn and H. Taube, J. Am. Chem. Soc., 1976, 98,
689–702; (b) S. S. Isied and H. Taube, Inorg. Chem., 1976,
15, 3070–3075.
32 (a) M. R. Camilo, C. R. Cardoso, R. M. Carlos and
A. B. P. Lever, Inorg. Chem., 2014, 53, 3694–3708;
(b) P. C. Ford, Chem. Sci., 2016, 7, 2964–2986; (c) G. Malouf
and P. C. Ford, J. Am. Chem. Soc., 1977, 99, 7213–7220.
33 (a) R. J. Singh, N. Hogg, J. Joseph and B. Kalyanaraman,
J. Biol. Chem., 1996, 271, 18596–18603; (b) M. Marazzi,
A. Lopez-Delgado, M. A. Fernandez-Gonzalez, O. Castano,
44 (a) M. E. Casida, C. Jamorski, K. C. Casida and
D. R. Salahub, J. Chem. Phys., 1998, 108, 4439–4449;
(b) R. E. Stratmann, G. E. Scuseria and M. J. Frisch,
J. Chem. Phys., 1998, 109, 8218–8224.
L. M. Frutos and M. Temprado, J. Phys. Chem. A, 2012, 116, 45 A. D. Becke, J. Chem. Phys., 1993, 98, 5648–5652.
7039–7049; (c) R. J. Singh, N. Hogg, J. Joseph and 46 C. T. Lee, W. T. Yang and R. G. Parr, Phys. Rev. B: Condens.
B. Kalyanaraman, FEBS Lett., 1995, 360, 47–51.
Matter Mater. Phys., 1988, 37, 785–789.
34 M. Nava, M. A. Martin-Drumel, C. A. Lopez, K. N. Crabtree, 47 (a) M. Cossi, G. Scalmani, N. Rega and V. Barone, J. Chem.
C. C. Womack, T. L. Nguyen, S. Thorwirth, C. C. Cummins,
J. F. Stanton and M. C. McCarthy, J. Am. Chem. Soc., 2016,
138, 11441–11444.
Phys., 2002, 117, 43–54; (b) S. Miertuš, E. Scrocco and
J. Tomasi, Chem. Phys., 1981, 55, 117–129.
48 P. Fuentealba, H. Preuss, H. Stoll and L. Vonszentpaly,
Chem. Phys. Lett., 1982, 89, 418–422.
35 (a) S. J. Blanksby and G. B. Ellison, Acc. Chem. Res., 2003,
36, 255–263; (b) E. R. Cohen, T. Cvitas, J. G. Frey, 49 A. D. Mclean and G. S. Chandler, J. Chem. Phys., 1980, 72,
B. Holmström, K. Kuchitsu, R. Marquardt, I. Mills, 5639–5648.
F. Pavese, M. Quack, J. Stohner, H. L. Strauss, M. Takami 50 N. M. O’Boyle, A. L. Tenderholt and K. M. Langner,
and A. J. Thor, Quantities, Units and Symbols in Physical J. Comput. Chem., 2008, 29, 839–845.
Chemistry, IUPAC Green Book, 3rd edn, IUPAC & RSC 51 (a) W. R. Browne, N. M. O’Boyle, J. J. McGarvey and
Publishing, Cambridge, 2007.
36 J. W. Ochterski, Thermochemistry in Gaussian, (accessed
November, 2018).
J. G. Vos, Chem. Soc. Rev., 2005, 34, 641–663; (b) M. Head-
Gordon, A. M. Grana, D. Maurice and C. A. White, J. Phys.
Chem., 1995, 99, 14261–14270.
37 M. D. Bartberger, J. D. Mannion, S. C. Powell, J. S. Stamler, 52 E. F. Pettersen, T. D. Goddard, C. C. Huang, G. S. Couch,
K. N. Houk and E. J. Toone, J. Am. Chem. Soc., 2001, 123,
8868–8869.
D. M. Greenblatt, E. C. Meng and T. E. Ferrin, J. Comput.
Chem., 2004, 25, 1605–1612.
Dalton Trans.
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