Nitric Oxide Dioxygenase Activity of a Nitrosyl Complex of Mn(II)-Porphyrinate in the Presence of Superoxide: Formation of a Mn(IV)-oxo Species through a Putative Peroxynitrite Intermediate

Article abstract of DOI:10.1021/acs.inorgchem.9b02359

A nitrosyl complex of Mn^II-porphyrinate, [(F₂₀TPP)Mn^II(NO)], 1 (F₂₀TPPH₂ = 5,10,15,20 tetrakis(pentafluorophenyl)porphyrin), was synthesized and characterized. Spectroscopic and structural characterization revealed complex 1 as a penta-coordinated Mn^II-nitrosyl with a linear Mn-N-O (180.0°) moiety. Complex 1 does not react with O₂. However, it reacts with superoxide (O₂ ^-) in THF at -80 °C to result in the corresponding nitrate (NO₃ ^-) complex, 2, via the formation of a presumed Mn^III-peroxynitrite intermediate. ESI-mass spectrometry and UV-visible and X-band EPR spectroscopic studies suggest the generation of Mn^IV-oxo species in the reaction through homolytic cleavage of the O-O bond of the peroxynitrite ligand as proposed in NOD activity. The intermediate formation of the Mn^III-peroxynitrite was further supported by the well accepted phenol ring nitration which resembles the biologically well-established tyrosine nitration.

Full text of DOI:10.1021/acs.inorgchem.9b02359

Article
Cite This: Inorg. Chem. XXXX, XXX, XXX−XXX
pubs.acs.org/IC
Nitric Oxide Dioxygenase Activity of a Nitrosyl Complex of Mn(II)-
Porphyrinate in the Presence of Superoxide: Formation of a Mn(IV)-
oxo Species through a Putative Peroxynitrite Intermediate
Baishakhi Mondal, Dibyajyoti Borah, Rakesh Mazumdar, and Biplab Mondal*
Department of Chemistry, Indian Institute of Technology Guwahati, Assam 781039, India
*
S Supporting Information
II
ABSTRACT: A nitrosyl complex of Mn -porphyrinate, [(F TPP)-
2
0
II
Mn (NO)], 1 (F TPPH = 5,10,15,20 tetrakis(pentafluorophenyl)-
20
2
porphyrin), was synthesized and characterized. Spectroscopic and
structural characterization revealed complex 1 as a penta-coordinated
II
Mn -nitrosyl with a linear Mn−N−O (180.0°) moiety. Complex 1
−
does not react with O . However, it reacts with superoxide (O ) in
2
2
−
THF at −80 °C to result in the corresponding nitrate (NO )
complex, 2, via the formation of a presumed Mn -peroxynitrite
3
III
intermediate. ESI-mass spectrometry and UV−visible and X-band EPR
IV
spectroscopic studies suggest the generation of Mn -oxo species in the
reaction through homolytic cleavage of the O−O bond of the
peroxynitrite ligand as proposed in NOD activity. The intermediate
III
formation of the Mn -peroxynitrite was further supported by the well accepted phenol ring nitration which resembles the
biologically well-established tyrosine nitration.
INTRODUCTION
immense importance to elucidate the undetected intermedi-
ate/s in the reaction.
■
Nitric oxide (NO) is known to play important roles in
mammalian biology including neurotransmission, immune
In the literature, the reaction of superoxo and peroxo
complexes of heme and nonheme iron, cobalt, and chromium
with NO are reported where the formation of the metal-
1
,2
response, etc.
However, overproduction of NO has
detrimental effects via the formation of secondary reactive
nitrogen species (RNS), for example, nitrogen dioxide (NO )
8
−10
peroxynitrite intermediates is implicated.
For instance, in
2
−
3,4
addition to the examples of formation of peroxynitrites in the
or peroxynitrite (ONOO ). The reaction of NO with a
III
−
•
−
reaction of oxy-heme (formally, Fe −O ) proteins with NO,
2
superoxide radical (O2 ), hydrogen peroxide (H O ), and/or
2
2
it has been reported recently that a Cr(IV)-peroxo complex
([Cr -(12-TMC)(O )(Cl)] ) {12-TMC = 1,4,8,11-tetra-
in the presence of transition metal ions is known to be
responsible for the formation of these RNS. Nitric oxide
IV
+
3
2
methyl-1,4,8,11-tetraazacyclotetradecane} reacts with NO to
dioxygenases (NODs) control the level of NO by converting it
III
−
5,6
lead to a Cr(III)-nitrato complex, ([Cr (12-TMC)(NO )-
3
into nitrate (NO ).
In NOD reactions, an iron(III)-
3
+
(
Cl)] ). On the other hand, the Cr(III)-superoxo analogue,
[Cr (14-TMC)(O )(Cl)] , upon reaction with NO yielded
the corresponding Cr(IV)-oxo complex, ([Cr -(14-TMC)-
(O)(Cl)] ) and NO . In both the reactions, the involvement
superoxo species reacts with NO to result in the biologically
III
+
−
−
2
benign NO3 ion. The formation of a ONOO ion has been
proposed as the intermediate in this transformation. It is
IV
+
IV
2
proposed that an oxo-ferryl, [Fe (O)] species formed in the
III
of a Cr(III)-peroxynitrite intermediate, [Cr (14-TMC)-
reaction via the homolytic cleavage of the O−O bond of the
+
11,12,9d,e
III
−
(OONO)(Cl)] was presumed.
The reaction of an
Fe -(ONOO ) intermediate. Such an oxo-ferryl species has
been evidenced spectroscopically in the reaction of myoglobin
III
Fe(III)-peroxo complex of the same ligand, [Fe (14-TMC)-
+
+
−
7
(O )] , with NO was also reported to proceed through the
2
13
with the ONOO ion. Though, in the literature, the
involvement of a proposed metal-peroxynitrite species was
exemplified in the reactions of NO with metal−oxygen species,
the direct evidence is still elusive. This is because of the very
short lifetime of metal-peroxynitrite. In addition, the evidence
of formation of high valent metal-oxo species from the
homolytic O−O bond cleavage of the metal-peroxynitrite
intermediate is also scarce because of very fast recombination
peroxynitrite intermediate. An example of the formation of a
presumed peroxynitrite intermediate in the reaction of the
cobalt-peroxo complex of a nonporphyrinate ligand with NO
1
4
was reported recently from our laboratory.
On the other hand, presumed metal-peroxynitrites are
reported to form in the reaction of a metal-nitrosyl and
dioxygen (O ). For example, the reaction of cobalt-nitrosyl
2
of the metal-oxo species with NO in the reaction cage to
2
−
result in NO . Hence, the reactivity study of metal-superoxo
Received: August 5, 2019
3
species with NO or a metal-nitrosyl with superoxide is of
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.inorgchem.9b02359
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
15
with O to yield NO2− was reported long before. The
with CHCl
(3 × 30 mL). The crude mass was column
2
3
III
chromatographed to result in complex [Mn (F TPP)Cl] as a red
reaction of a nonheme dinitrosyliron complex with O resulted
20
2
2
3b
−
16
solid.
Yield: 0.11 g (ca. 40%). Elemental analyses for
in a NO complex. A Cu(I)-nitrosyl complex afforded the
NO2 product in the presence of O via a presumed
peroxynitrite intermediate. In addition, the {Cu(NO)}
complex in the presence of H O was also found to result in a
3
−
C H N F ClMn, calcd (%): C, 49.72; H, 0.76; N, 5.27. Found
4
4
8
4 20
2
−1
17
10
(%): C, 49.80; H, 0.81; N, 5.39. UV−visible (THF): 429 nm (ε/M
−1 5 −1 −1 4
cm , 1.11 × 10 ) and 561 nm (ε/M cm , 1.34 × 10 ). FT-IR (in
2
2
KBr): 1651, 1516, 1492, 1426, 1340, 1165, 1085, 1059, 1011, 989,
copper-nitrato complex through a presumed Cu(I)-peroxyni-
−1
9
(
43, and 761 cm . Mass (m/Z) calcd: 1026.98. Found: 1027.01
18
III
trite intermediate formation.
molecular ion peak for [Mn (F TPP)]). Crystal data:
2
0
III
We report herein the synthesis and characterization of a five
coordinated manganese-nitrosyl, [(F TPP)Mn(NO)] (1),
[Mn (F TPP)Cl], CCDC No.1911995. C H F ClN Mn, M =
20 44 8 20 4
1062.93, tetragonal (I4/m), a = 17.639(3), b = 17.639(3), c =
9.583(2) Å, α = 90.00°, β = 90.00°, γ = 90.00°, V = 2981.6(12) Å , Z
2
0
−
3
and its reactivity with superoxide (O ) where the formation
2
−
3
−1
=
2, Dc = 1.184 g cm , μ = 0.357 mm , T = 293(2) K, 1399
of peroxynitrite intermediate is implicated. Spectroscopic
IV
reflections, 570 independent, R(F) = 0.1247 [I > 2δ(I)], R(int) =
.1689, wR(F2) = 0.2537 (all data), GOF = 1.164.
evidence suggests the formation of the [(F TPP)Mn (O)]
20
0
species in the reaction. Finally, this species resulted in the
II
Synthesis of Complex 1, [Mn (F TPP)(NO)]. Complex 1 was
−
20
corresponding NO3 product upon recombination with NO2.
prepared following the reported procedure with minor modifica-
23c
tion. Triethylamine (0.76 g, 7.50 mmol) was added to a methanolic
(10 mL) solution of hydroxylamine hydrochloride (0.52 g, 7.50
mmol) at 0 °C. A fresh solution of hydroxylamine was added to the
EXPERIMENTAL SECTION
■
Materials and Methods. All reagents and solvents of reagent
grade were purchased from commercial sources and used as received
except as specified. All the reactions were performed under inert
conditions unless specified. Deoxygenation of the distilled solvents
and solutions was effected by repeated vacuum/purge cycles or
bubbling with argon. UV−visible spectra were monitored on an
Agilent Technologies Cary 8454 UV−visible spectrophotometer. FT-
IR spectra of the samples were taken on a PerkinElmer
spectrophotometer, and the samples were prepared either as KBr
pellets or in solution in a KBr cell. A 400 MHz or 600 MHz Varian
III
CH Cl solution of the [Mn (F TPP)Cl] complex (1.59 g, 1.50
2
2
20
mmol) at −20 °C. Then, complex 1 precipitated out of solution as red
crystals in a period of 3−4 days at low temperature and was isolated
by filtration. Yield: 1.11 g, ∼70%. Elemental analyses for
C H N OF Mn, calcd (%): C, 49.98; H, 0.76; N, 6.62. Found
44
8
5
20
−
1
(
%): C, 50.06; H, 0.73; N, 6.70. UV−visible (THF): 415 nm (ε/M
−1 5 −1 −1 4
cm , 1.04 × 10 ), 532 nm (ε/M cm , 1.02 × 10 ), and 564 nm
(
1
−
1
−1
3
ε/M cm , 3.95 × 10 ). FT-IR (in KBr): 1763, 1650, 1516, 1489,
1 1
−
344, 1195, 1165, 1079, 1059, 987, 941, and 762 cm . H NMR
1
(400 MHz, d -DMSO): δ
CCDC No. 1911994. C H Cl F N O Mn, M = 1427.21, tetragonal
9.09 (s, 8H). Crystal data: complex 1,
FT spectrometer was used for H NMR spectra recording. Chemical
6
ppm
shifts (ppm) were referenced either with an internal standard (Me Si)
48 16
8
20
6
2
4
(
I4/m), a = 16.8084(4), b = 16.8084(4), c = 9.5523(4) Å, α= 90.00°,
or to the residual solvent peaks. The X-band Electron Paramagnetic
Resonance (EPR) spectra were recorded on a JES-FA200 ESR
spectrometer, at room temperature as well as liquid nitrogen
temperature with microwave power, 0.998 mW; microwave frequency,
3
−3
β = 90.00°, γ = 90.00°, V = 2698.74(17) Å , Z = 2, Dc = 1.756 g cm ,
−
1
μ = 0.757 mm , T = 101(1) K, 1259 reflections, 1126 independent,
R(F) = 0.0477 [I > 2δ(I)], R(int) = 0.0535, wR(F2) = 0.1292 (all
data), GOF = 1.032.
9
.14 GHz; and modulation amplitude, 2. Elemental analyses were
III
Synthesis of Complex 2, [Mn (F TPP)(NO )]. Complex 1 (0.53 g,
.5 mmol) was dissolved in 20 mL of dry THF, and the solution was
obtained from a PerkinElmer Series II Analyzer.
20
3
0
Single crystals were grown by the slow evaporation of CHCl and
3
cooled at −80 °C. To this cold solution, 1 equiv of potassium
superoxide in the presence of 18-crown-6 (5 equiv) in THF was
added at −80 °C and stirred for 2 h. The solution was slowly warmed
to room temperature. The red solution changed to dark red. Then the
solution was vacuum-dried (0.41 g, ∼75% yield). Elemental analyses
CH Cl2 solutions of the ligand and complexes, respectively. The
2
intensity data were collected using a Bruker SMART APEX-II CCD
diffractometer, equipped with a fine focus 1.75 kW sealed tube Mo Kα
radiation (λ = 0.71073 Å) at 293(3) K, with increasing ω (width of
0
.3° per frame) at a scan speed of 3 s/frame. The SMART software
was used for data acquisition. Data integration and reduction were
undertaken with SAINT and XPREP software. Multiscan empirical
absorption corrections were employed to the data using the program
SADABS. Structures were solved by direct methods using SHELXS-
2
2
Windows.
Syntheses. Ligand [(5,10,15,20-tetrakis(pentafluoropheny1)-
porphyrin)], (F TPPH ). The ligand F TPPH was prepared by
for C44H N O F20Mn, calcd (%): C, 48.51; H, 0.74; N, 6.43. Found
8 5 3
19
−1
(%): C, 48.59; H, 0.70; N, 6.56. UV−visible (THF): 458 nm (ε/M
−1 5 −1 −1 4
cm , 0.54 × 10 ), 572 nm (ε/M cm , 0.77 × 10 ). FT-IR (in
20
KBr): 1650, 1525, 1492, 1384, 1335, 1162, 1073, 1052, 988, 937, 800,
2
−1
016 and refined with full-matrix least-squares on F using SHELXL-
and 759 cm . Mass (m/Z) calcd: 1088.97. Found: 1088.88
21
016/6. 2S2tructural illustrations have been drawn with ORTEP-3 for
(molecular ion peak).
III
Complex 3, [Mn (F20TPP)(OH)], 3,3′,5,5′-tetra-tert-butyl-[1,1′-
biphenyl]-2,2′-diol and 2,4-ditertiarybutyl-6-nitrophenol. Complex
1 (1.06 g, 1 mmol) and 2,4-di-tert-butyl phenol (1.03 g, 5 mmol) were
dissolved in 20 mL of dry and degassed THF. The mixture was cooled
to −80 °C. To this degassed solution, 1 equiv of potassium
superoxide in the presence of 18-crown-6 (5 equiv) in THF was
added at −80 °C and stirred for 2 h. The reaction mixture was then
brought to room temperature and dried under reduced pressure. The
solid mass was then subjected to column chromatography using a
silica gel column to obtain pure 3,3′,5,5′-tetra-tert-butyl-[1,1′-
biphenyl]-2,2′-diol, 2,4-ditertiarybutyl-6-nitrophenol, and complex 3.
3,3′,5,5′-tetra-tert-butyl-[1,1′-biphenyl]-2,2′-diol. Yield: 0.08 g
2
0
2
20
2
mixing 2,3,4,5,6-pentafluorobenzaldehyde (3.92 g, 20 mmol) and
freshly distilled pyrrole (1.34 g, 20 mmol) in 37 mL of propionic acid
23a
following the reported procedure of porphyrin synthesis.
The
solution was refluxed for 3 h and cooled to room temperature.
Neutralization of the reaction mixture was done by aqueous Na CO
2
3
to precipitate out the crude product. This crude product was purified
by column chromatography as purple crystals (0.49 g, ca. 10% yield).
Elemental analyses for C H F N , Calcd (%): C, 54.23; H, 1.03; N,
4
4
10 20
4
5
2
.75. Found (%): C, 54.33; H, 1.07; N, 5.84. FT-IR (in KBr): 3318,
923, 1648, 1514, 1500, 1435, 1078, 989, 919, 807, 772, 757, and 724
(∼20%). Elemental analyses for C28
10.31. Found (%): C, 81.98; H, 10.33. H NMR (400 MHz, CDCl
δppm 7.39 (s, 2 H), 7.12 (s, 2 H), 5.23 (s, 2 H), 1.45 (s, 18 H), and
H
O
2
, calcd (%): C, 81.90; H,
42
−
1
1
1
cm . H NMR (600 MHz, CDCl ): δppm, 8.93 (s, 8H). Mass (m/Z)
3
):
3
calcd: 974.06. Found: 975.03 (M+1).
III
13
Synthesis of [Mn (F TPP)Cl]. The ligand F TPPH (0.24 g, 0.25
1.32 (s, 18 H). C NMR (100 MHz, CDCl ): δ
150.0, 143.2,
20
20
2
3
ppm
mmol), Mn(OAc) ·4H O (0.61 g, 2.50 mmol), and sodium chloride
136.5, 125.5, 125.0, 122.6, 35.4, 34.7, 31.9, and 29.9. Mass (m/Z)
calcd: 410.32. Found: 409.31 (M − 1).
2
2
(
0.09 g, 1.5 mmol) in CHCl (12 mL) and acetic acid (12 mL) was
3
taken in a 100 mL round-bottom flask. The mixture was refluxed at
20 °C for 6 h. The solution was cooled and filtered. A total of 60 mL
of water was poured into the filtrate. The solution was then extracted
2,4-Di-tert-butyl-6-nitrophenol. Yield: 0.10 g (∼40%), Elemental
analyses for C H NO , calcd (%): C, 66.91; H, 8.42; N, 5.57. Found
1
1
4
21
3
1
(%): C, 66.86; H, 8.45; N, 5.66. H NMR (600 MHz, CDCl ): δ
3
ppm
B
DOI: 10.1021/acs.inorgchem.9b02359
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
1
.32 (s, 9H), 1.45 (s, 9H), 5.22 (s, 1H), 7.12 (s, 1H), 7.40 (s, 1H).
1
3
C NMR (150 MHz, CDCl ): δ
29.7, 31.6, 34.5, 35.2, 122.3,
3
ppm
1
24.8, 125.3, 136.2, 143.0, 149.8. ESI-Mass (m/z) calcd: 251.15.
Found: 250.41 (M − 1).
Complex 3. Yield: 0.68 g (∼65%). Elemental analyses for
C H N OF Mn, Calcd (%): C, 50.60; H, 0.87; N, 5.36. Found
44
9
4
20
(
1
M
%): C, 50.63; H, 0.89; N, 5.34. FT-IR (in KBr): 3530, 1650, 1490,
−
1
423, 1163, 1087, 990, 761 cm . UV−visible (THF): 430 nm (ε/
−
1
−1
5
−1
−1
4
cm , 0.35 × 10 ), 569 nm (ε/M cm , 0.49 × 10 ).
RESULTS AND DISCUSSION
The ligand was prepared following typical reported methods of
porphyrin synthesis and characterized using spectroscopic
■
23a
techniques (Supporting Information; Figures S1−S4). The
II
Mn -nitrosyl complex, {(F TPP)Mn(NO)} (1), has been
20
prepared from the reaction of {(F TPP)Mn(Cl)} with
2
0
hydroxylamine using the reported literature procedure with a
little modification (Supporting Information; Figures S9−
Figure 2. UV−visible spectral monitoring of complex 1 (black) and
2
3c
S12).
It was characterized by various spectroscopic
after addition of KO in crown ether to result in complex 2 (red) in
2
techniques as well as by single crystal structure determination
THF at −80 °C.
(
Supporting Information; Tables S1−S3). The ORTEP
diagram of complex 1 is given in Figure 1. It revealed complex
The 426 nm band was transient and disappeared with time,
whereas the intensity of the absorption at 458 nm increases.
The final decomposition product was isolated and charac-
−
III
terized as the corresponding nitrate (NO ) complex of Mn -
3
porphyrinate complex 2. It shows an absorption band at 458
nm. The transient 426 nm band is attributed to the absorption
IV
of the corresponding Mn -oxo species, which is formed via the
III
homolytic O−O bond cleavage of a presumed Mn -
peroxynitrite intermediate (Scheme 1). In the literature, it
IV
has been reported that Mn -oxo complexes absorb at the
range of 420−430 nm and owing to their very unstable nature,
III
convert rapidly to the corresponding Mn -porphyrinate.
Newcomb et al. reported the formation of the same
IV
[
(F TPP)Mn O] species in acetonitrile solution through
2
0
III
laser flash photolysis of [(F TPP)Mn (ClO )], and that
shows absorption at 422 nm.
2
0
3
2
5
The minor shift in absorption wavelength is perhaps because
of the change of solvent and temperature.
II
Figure 1. ORTEP diagram of complex 1 (50% thermal ellipsoid plot;
H atoms and solvent molecules are removed for clarity).
It is to be noted that when [(F TPP)Mn ] was made to
2
0
react with KO in THF at −80 °C, the absorption bands in the
2
UV−visible spectrum appeared at 451 and 569 nm,
respectively (Supporting Information, Figure S30), and these
bands are stable at that temperature for hours. In the reaction
of the [(F TPP)Mn(NO)] and KO in THF at −80 °C, we
II
1
as a five coordinated nitrosyl complex of Mn -porphyrinate.
It is to be noted that though there are many examples of
structurally characterized six coordinated nitrosyl complexes of
Mn -porphyrinates, the number for five coordinated ones is
2
0
2
have not observed any such bands in the UV−visible
monitoring. Hence, the possibility of the replacement of the
NO group by superoxide could be ruled out in the reaction of
[(F TPP)Mn(NO)] and KO .
II
much less. The metric parameters (Supporting Information;
Tables S1−S3) are within the range of reported analogous
complexes. The N−O bond distance and Mn−N−O bond
angles are 1.132(10) Å and 180.0°, respectively. These values
appear in the reported range for analogous complexes. For
instance, in the case of the nitrosyl complex of (5,10,15,20-
tetratolylporphinato)manganese(II), the Mn−N−O bond
angle is reported as 177.8(3)° and the N−O distance is
2
0
2
In FT-IR spectroscopy, complex 1 in a KBr pellet displays
−
1
nitrosyl stretching at 1763 cm (Figure 3). This is in
agreement with the reported nitrosyl stretching in analogous
II
complexes. For example, [(TPP)Mn NO] shows nitrosyl
−1
26
stretching at 1760 cm . We attempted to monitor the FT-
IR spectral change during the reaction; however, we ended up
2
4
−1
1
.160(3) Å.
with a spectrum where the 1763 cm band disappeared with
−
1
The complex 1 in THF solution at −80 °C shows
absorption bands at 415, 532, and 564 nm (Figure 2 and
Supporting Information, Figure S10). The addition of a
precooled THF solution of KO in crown ether resulted in the
decrease of the 415 nm band along with a concomitant
formation of new absorption bands at 426 and 458 nm (Figure
the appearance of a new stretching at ∼1430 and 1261 cm .
−
These are assignable to the corresponding NO stretchings of
3
27
complex 2 (Supporting Information, Figure S13b). When the
FT-IR spectrum of the isolated complex 2 was recorded in KBr
2
−
1
pellets, a stretching at 1384 cm was observed (Supporting
Information, Figure S13a). It is to be noted that in the case of
2
; Scheme 1).
[(TPP)Mn(ONO )], the nitrate stretching appeared at ∼1470
2
C
DOI: 10.1021/acs.inorgchem.9b02359
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
Scheme 1
assignable to the [(F TPP)Mn(O)] moiety (calcd.1042.98;
2
0
Figure 4).
Figure 3. FT-IR spectrum of complex 1 in KBr.
−
1
and 1284 cm . However, when the spectrum was recorded in
KBr pellets, three bands were observed at 1474, 1385, and
−
1
−1
1
286 cm . The appearance of the 1384 cm band was
−
Figure 4. ESI-mass spectrum of the reaction mixture obtained from
attributed to the stretching of free NO , which is formed in
the reaction of [(TPP)Mn(O-NO )] with KBr.
3
the reaction of complex 1 and KO (in crown ether) in THF at −80
2
7
2
In
2
°
C. [Inset: (a) simulated and (b) experimental isotopic distribution
pattern.]
comparison with the other reported analogous complexes,
the bands at 1430 and 1261 cm− are assigned to the ν (NO )
1
a
2
and ν (NO ), respectively, of the uncoordinated NO group in
s
2
2
1
the [Mn( η-ONO )] moiety, suggesting the presence of a
The isotopic distribution pattern in the observed spectrum
2
27
nitrate ion in O-coordinated monodentate fashion. The
matches well with the simulated one (Figure 4). Thus, the ESI
mass spectrometry suggests the formation of a [(F TPP)Mn-
stretching corresponding to the coordinated O−N fragment
20
−1
appears in the range of ∼1000 cm . However, we have not
(O)] intermediate. In the mass spectrum of the decomposition
product, the molecular ion peak appeared at m/z 1088.88
corresponding to a [(F TPP)Mn(NO )] unit (calcd m/z,
observed that in the present case perhaps because of masking
27
by the presence of strong porphyrin stretching bands.
2
0
3
The ESI mass spectrum of complex 1 was populated by the
molecular ion peak at m/z 1027.15 assignable to the
1088.97; complex 2; Supporting Information, Figure S14).
In X-band EPR spectroscopy, complex 1 appeared silent as
expected for a low spin Mn center with an antiferromagneti-
II
[
(F TPP)Mn] moiety (calcd. m/z = 1026.98; Supporting
2
0
Information, Figure S11). This is attributed to the loss of an
axial nitrosyl group under the experimental conditions.
cally coupled nitrosyl group. However, the frozen (at 77 K)
reaction mixture obtained from the reaction of complex 1 in
28
However, the ESI-mass spectrum of the reaction mixture
THF at −80 °C with KO displayed a strong, broad EPR signal
2
obtained from the reaction of complex 1 with KO in THF at
with g ∼ 5.26 and a weak one at 2.27, respectively. This is
2
IV
−80 °C shows the molecular ion peak at 1043.07, which is
attributed to the presence of a high spin Mn center (S = 3/2)
D
DOI: 10.1021/acs.inorgchem.9b02359
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
2
9
IV
in a square pyramidal geometry (Figure 5). A spin
intermediate, which gives rise to the Mn -oxo and NO
following the NOD pathway.
2
quantification experiment with respect to the authentic
The isolation and characterization of complex 2 as the
decomposition product from the reaction of complex 1 and
III
KO2 also supports the formation of a Mn -peroxynitrite
27,28a
intermediate.
It is well established that the very short
lifetime of the metal-peroxynitrite complexes precluded their
spectral analyses. Therefore, the chemical evidence was sought
to establish the intermediate formation of peroxynitrite in said
reaction. When the reaction was carried out in the presence of
2
2
,4-ditertiarybutylphenol, nitration was observed leading to
,4-ditertiarybutyl-6-nitrophenol formation in ca. 40% yield
with a fraction of oxidative product bis-phenol (ca. 20%). It is
to be noted that phenol nitration/oxidative coupling has been
used extensively as evidence to establish the presence of metal-
peroxynitrite species. This reaction has considerable impor-
tance as this resembles the biologically well-known tyrosine
3a,b,4,33
nitration.
In addition, complex 1 itself does not react
with 2,4-ditertiarybutylphenol under the reaction conditions.
In the NOD reactivity of heme-iron complexes, it is
proposed that metal-peroxynitrite ion mediated nitration or
Figure 5. X-band EPR spectrum of the intermediate formed during
the reaction between complex 1 and KO (in crown ether) in THF at
2
7
7 K.
IV
oxidation proceeds through the formation of the Fe -oxo
IV
intermediate along with NO . The phenolic substrates reduce
[
[
Mn O] sample generated in the reaction of the
2
IV
III
the Fe -oxo species rapidly to the Fe state to result in a
(F TPP)MnCl] complex and mCPBA suggests the presence
2
0
phenoxyl radical. This radical then either combines with NO2
to result in nitro-phenol or two phenoxyl radicals couple to
of ∼60% of the same species in the frozen (at 77 K) sample
obtained from the reaction of complex 1 and KO in THF at
2
yield corresponding bis-phenol product. In the present case,
−
80 °C (Supporting Information, Figure S32a,b). [(TMP)-
IV
IV
the spectral evidence suggests the formation of Mn -oxo
Mn (O)] was reported to display a strong and broad signal at
29
species in the reaction of complex 1 with KO . Recently, it has
g ∼ 4 and a weak one at g ∼ 2.21. These g values, however,
2
III
IV
been reported that a Cr -superoxo complex of tetramethylated
are in the range of the reported Mn O complexes. For
IV
2+
cyclam ligand reacts with NO in acetonitrile at −40 °C to
instance, g ∼ 5.76 signal in the case of [Mn (O)(N py)]
eff
4
IV
result in the formation of Cr -oxo species via homolytic O−O
[
N py = (N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)-
4
30
bond cleavage of the presumed Cr-peroxynitrite intermedi-
methylamine)].
9d
IV
3−
ate. Earlier, cobalt nitrosyl [(F TPP)Co(NO)] was found to
In the case of [Mn (H buea)(O)] species [H buea
=
8
3
3
show NOD reactivity in the presence of H O through the
tris[(N′-tert-butylureaylato)-N-ethylene]aminato)], the g val-
2
2
III
•
27a
31
formation of a transient [(F TPP)Co −O ] radical.
ues appeared at 5.15, 2.44, and 1.63. To confirm the presence
8
IV
Complexes of Cu and Cr were also reported in the literature
to display NOD activity. However, to the best of our
knowledge, this result demonstrates the first example of a
nitrosyl complex of Mn-porphyrin, which displays NOD
of Mn center, an authentic sample was prepared from the
reaction of [(F TPP)MnCl] with mCPBA in THF at −80 °C,
2
0
and the EPR spectrum was recorded at 77 K and compared
with the observed one (Supporting Information, Figure S24).
It was found that both the spectra are in agreement. It should
be worth mentioning that Mn(II) high spin (S = 3/2)
complexes show signals at g ∼ 5.95 and 2.10 in X-band EPR
reactivity in the presence of KO . The spectral evidence
2
IV
clearly suggests the involvement of a Mn -oxo intermediate in
the NOD reactivity of complex 1.
3
2
spectrum. To confirm our assignment of the observed
II
CONCLUSIONS
signals, the EPR of the authentic [(F TPP)Mn ] was
■
2
0
II
recorded in THF at 77 K (Supporting Information, Figures
Thus, the nitrosyl complex of Mn -porphyrinate, [(F20TPP)-
II
−
S25, S26). The respective signals appeared at g ∼ 6.10 and
Mn (NO)], 1, upon reaction with superoxide (O
2
) in THF at
−
2
.15.
−80 °C resulted in the corresponding nitrate (NO ) complex
3
III
Thus, UV−visible, ESI-mass, and X-band EPR spectral
2 via the formation of a presumed Mn -peroxynitrite
intermediate. ESI-mass spectrometry, UV−visible, and X-
band EPR spectroscopic studies suggest the generation of
IV
studies suggest the formation of a Mn -oxo intermediate in
the reaction of complex 1 with KO . We have tried to record
2
IV
the resonance Raman spectrum of the intermediate but could
not succeed. This is perhaps because of thermal instability of
the intermediate along with its photodecomposition under
Mn -oxo species in the reaction through homolytic cleavage of
the O−O bond of the peroxynitrite ligand as proposed in
III
NOD activity. The intermediate formation of the Mn -
IV
laser light. A probable mechanism of formation of the Mn -
peroxynitrite was further supported by the well accepted
phenol ring nitration, which resembles the biologically well-
established tyrosine nitration.
II
−
oxo species in the reaction of Mn -nitrosyl complex 1 with O
2
is depicted in Scheme 1. According to the widely accepted
III
−
mechanism of NOD activity, the Fe -(O ) species reacts
2
III
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.9b02359.
with NO to result in the Fe -peroxynitrite intermediate. In the
■
subsequent step, the peroxynitrite ligand undergoes homolytic
*
S
IV
7
O−O bond cleavage to generate Fe -oxo species and NO . In
2
II
−
the present study, thus the reaction of Mn -nitrosyl with O is
2
III
presumably resulting in the corresponding Mn -peroxynitrite
E
DOI: 10.1021/acs.inorgchem.9b02359
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Figures S1−S32 and Tables S1−S3 (PDF)
Article
281. (c) Tocheva, E. I.; Rosell, F. I.; Mauk, A. G.; Murphy, M. E. Side-
on copper-nitrosyl coordination by nitrite reductase. Science 2004,
Accession Codes
304, 867.
CCDC 1911994−1911995 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
(
6) (a) Gardner, P. R.; Gardner, A. M.; Martin, L. A.; Salzman, A. L.
Nitric oxide dioxygenase: An enzymic function for flavohemoglobin.
Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 10378. (b) Schopfer, M. P.;
Mondal, B.; Lee, D.-H.; Sarjeant, A. A. N.; Karlin, K. D. Heme/O
NO Nitric Oxide Dioxygenase (NOD) Reactivity: Phenolic nitration
via a putative heme-peroxynitrite intermediate. J. Am. Chem. Soc.
009, 131, 11304.
7) Su, J.; Groves, J. T. Mechanisms of peroxynitrite interactions
with heme proteins. Inorg. Chem. 2010, 49, 6317.
8) (a) Wick, P. K.; Kissner, R.; Koppenol, W. H. Synthesis and
/
2
•
2
(
AUTHOR INFORMATION
Corresponding Author
Phone: (+) 91-361-258-2317. Fax: (+)91-361-258-2339. E-
mail: biplab@iitg.ac.in.
■
*
(
c h a r a c t e r i z a t i o n o f t r i s ( t e t r a e t h y l a m m o n i u m ) -
pentacyanoperoxynitrito-cobaltate(III). Helv. Chim. Acta 2000, 83,
748. (b) Maiti, D.; Lee, D.-H.; Narducci Sarjeant, A. A.; Pau, M. Y.
M.; Solomon, E. I.; Gaoutchenova, K.; Sundermeyer, J.; Karlin, K. D.
Reaction of a copper-dioxygen Complex with nitrogen monoxide
ORCID
Biplab Mondal: 0000-0002-0594-6749
Notes
The authors declare no competing financial interest.
(
•NO) leads to a copper(II)-peroxynitrite species. J. Am. Chem. Soc.
008, 130, 6700.
9) (a) Goodwin, J. A.; Coor, J. L.; Kavanagh, D. F.; Sabbagh, M.;
2
(
ACKNOWLEDGMENTS
The authors would like to thank the Department of Science
and Technology, India for financial support (EMR/2014/
Howard, J. W.; Adamec, J. R.; Parmley, D. J.; Tarsis, E. M.; Kurtikyan,
T. S.; Hovhannisyan, A. A.; Desrochers, P. J.; Standard, J. M. Catalytic
dioxygen activation by (nitro)(meso-tetrakis(2-N-methylpyridyl)-
porphyrinato)cobalt(III) cation derivatives electro-statically immobi-
lized in nafion films: An experimental and DFT investigation. Inorg.
Chem. 2008, 47, 7852. (b) Kurtikyan, T. S.; Ford, P. C.
Hexacoordinate oxyglobin models Fe(Por)(NH )(O ) react with
■
0
00291) and DST-FIST for the single crystal X-ray diffraction
facility. B.M., D.B., and R.M. extend their sincere thanks to the
CIF, IIT Guwahati for instrumental facilities.
3
2
1
NO to form only the nitrato analogs Fe(Por)(NH )(η -ONO ), even
3
2
DEDICATION
Dedicated to Prof. G. K. Lahiri on his 60th birthday.
■
at ∼ 100 K. Chem. Commun. 2010, 46, 8570. (c) Kurtikyan, T. S.;
Eksuzyan, S. R.; Goodwin, J. A.; Hovhannisyan, G. S. Nitric oxide
interaction with oxy-coboglobin models containing trans-pyridine
ligand: two reaction pathways. Inorg. Chem. 2013, 52, 12046.
REFERENCES
■
(
d) Yokoyama, A.; Cho, K.-B.; Karlin, K. D.; Nam, W. Reactions of
(
1) Ignarro, L. J. Nitric Oxide: Biology and Pathobiology; Academic
Press: San Diego, 2000.
a chromium(III)-superoxo complex and nitric oxide that lead to the
formation of chromium(IV)-oxo and chromium(III)-nitrito com-
plexes. J. Am. Chem. Soc. 2013, 135, 14900. (e) Yokoyama, A.; Han, J.
E.; Cho, J.; Kubo, M.; Ogura, T.; Siegler, M. A.; Karlin, K. D.; Nam,
W. Chromium(IV)-peroxo complex formation and its nitric oxide
dioxygenase reactivity. J. Am. Chem. Soc. 2012, 134, 15269.
(
2) (a) Moncada, S.; Palmer, R. M. J.; Higgs, E. A. Nitric oxide:
physiology, pathophysiology and pharmacology. Pharmacol. Rev.
991, 43, 109. (b) Butler, A. R.; Williams, D. L. H. The physiological
1
role of nitric oxide. Chem. Soc. Rev. 1993, 22, 233. (c) Feelisch, M.;
Stamler, J. S. Methods in Nitric Oxide Research; John Wiley and Sons;
Chichester, England, 1996. (d) Jia, L.; Bonaventura, C.; Bonaventura,
J.; Stamler, J. S. S-nitrosohaemoglobin: a dynamic activity of blood
involved in vascular control. Nature 1996, 380, 221. (e) Gladwin, M.
T.; Lancaster, J. R.; Freeman, B. A.; Schechter, A. N. Nitric oxide’s
reactions with hemoglobin: a view through the SNO-storm. Nat. Med.
(10) Kumar, P.; Lee, Y.-M.; Park, Y. J.; Siegler, M. A.; Karlin, K. D.;
Nam, W. Reactions of Co(III)-nitrosyl complexes with superoxide
and their mechanistic insights. J. Am. Chem. Soc. 2015, 137, 4284.
(11) Hughes, M. N.; Nicklin, H. G.; Sackrule, W. A. C. The
chemistry of peroxonitrites. Part III. The reaction of peroxonitrite
with nucleophiles in alkali, and other nitrite producing reactions. J.
Chem. Soc. A 1971, 3722.
2
(
003, 9, 496.
3) (a) Radi, R. Nitric oxide, oxidants, and protein tyrosine nitration.
(12) (a) Herold, S.; Koppenol, W. H. Peroxynitritometal complexes.
Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 4003. (b) Ford, P. C.; Wink,
D. A.; Stanbury, D. M. Autoxidation kinetics of aqueous nitric oxide.
FEBS Lett. 1993, 326, 1. (c) Tran, N. G.; Kalyvas, H.; Skodje, K. M.;
Coord. Chem. Rev. 2005, 249, 499. (b) Roncaroli, F.; Videla, M.; Slep,
L. D.; Olabe, J. A. New features in the redox coordination chemistry
+
•
−
Hayashi, T.; Moe
Kirschenbaum, L. J.; Kim, E. Phenol nitration induced by an
Fe(NO)2}10 dinitrosyl iron complex. J. Am. Chem. Soc. 2011, 133,
184.
4) (a) Goldstein, S.; Lind, J.; Merenyi, G. Chemistry of
peroxynitrites as compared to peroxynitrates. Chem. Rev. 2005, 105,
457. (b) Pacher, P.; Beckman, J. S.; Liaudet, L. Nitric oxide and
peroxynitrite in health and disease. Physiol. Rev. 2007, 87, 315.
c) Blough, N. V.; Zafiriou, O. C. Reaction of superoxide with nitric
oxide to form peroxonitrite in alkaline aqueous solution. Inorg. Chem.
985, 24, 3502. (d) Nauser, T.; Koppenol, W. H. The rate constant of
̈
nne-Loccoz, P.; Callan, P. E.; Shearer, J.;
of metal nitrosyls {M-NO ; M-NO ; MNO (HNO)}. Coord. Chem.
Rev. 2007, 251, 1903.
(13) Yokoyama, A.; Han, J. E.; Karlin, K. D.; Nam, W. An
isoelectronic NO dioxygenase reaction using a nonheme iron(III)-
peroxo complex and nitrosonium ion. Chem. Commun. 2014, 50,
1742.
(14) Saha, S.; Ghosh, S.; Gogoi, K.; Deka, H.; Mondal, B.; Mondal,
B. Reaction of a Co(III)-peroxo complex and NO: Formation of a
putative peroxynitrite intermediate. Inorg. Chem. 2017, 56, 10932.
(15) (a) Clarkson, S. G.; Basolo, F. Reactions of some cobalt nitrosyl
complexes with oxygen. J. Chem. Soc., Chem. Commun. 1972, 119, 670.
(b) Clarkson, S. G.; Basolo, F. Study of the reaction of some cobalt
nitrosyl complexes with oxygen. Inorg. Chem. 1973, 12, 1528.
(16) Skodje, K. M.; Williard, P. G.; Kim, E. Conversion of
{
1
(
2
(
1
the reaction of superoxide with nitrogen monoxide: approaching the
diffusion limit. J. Phys. Chem. A 2002, 106, 4084.
(
5) (a) Doyle, M. P.; Hoekstra, J. W. Oxidation of nitrogen oxides
by bound dioxygen in hemoproteins. J. Inorg. Biochem. 1981, 14, 351.
b) Cooper, C. E.; Torres, J.; Sharpe, M. A.; Wilson, M. T. Nitric
1
0
{Fe(NO) } dinitrosyl iron to nitrato iron(III) species by molecular
oxygen. Dalton Trans 2012, 41, 7849.
2
(
oxide ejects electrons from the binuclear centre of cytochrome c
oxidase by reacting with oxidised copper: a general mechanism for the
interaction of copper proteins with nitric oxide? FEBS Lett. 1997, 414,
(17) Park, G. Y.; Deepalatha, S.; Puiu, S. C.; Lee, D.-H.; Mondal, B.;
Narducci Sarjeant, A. A.; del Rio, D.; Pau, M. Y. M.; Solomon, E. I.;
Karlin, K. D. A peroxynitrite complex of copper: formation from a
F
DOI: 10.1021/acs.inorgchem.9b02359
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
copper-nitrosyl complex, transformation to nitrite and exogenous
phenol oxidative coupling or nitration. JBIC, J. Biol. Inorg. Chem.
(33) Kalyanaraman, B. Nitrated lipids: A class of cell-signaling
molecules. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 11527.
2
(
009, 14, 1301.
18) Kalita, A.; Kumar, P.; Mondal, B. Reaction of a copper(II)-
nitrosyl complex with hydrogen peroxide: putative formation of a
copper(I)-peroxynitrite intermediate. Chem. Commun. 2012, 48, 4636.
(
19) SMART; SAINT; XPREP; Siemens Analytical X-ray Instru-
ments Inc.: Madison, WI, 1995.
20) Sheldrick, G. M. SADABS: Software for Empirical Absorption
(
Correction University of Gottingen, Institut fur Anorganische
Chemieder Universitat: Gottingen, Germany, 1999.
(
21) Sheldrick, G. M. SHELXS-2014; University of Gottingen:
Germany.
(
(
22) Farrugia, L. J. J. Appl. Crystallogr. 1997, 30, 565.
23) (a) Adler, A. D.; Longo, F. R.; Finarelli; Goldmacher, J.;
Assour, J.; Korsakoff, L. A simplified synthesis for meso-
tetraphenylporphine. J. Org. Chem. 1967, 32, 476. (b) Rothemund,
P.; Menotti, A. R. Porphyrin Studies. V. The Metal Complex Salts of
α,β,γ,δ-Tetraphenylporphine. J. Am. Chem. Soc. 1948, 70, 1808.
(
c) Choi, In-K.; Liu, Y.; Wei, Z.; Ryan, M. D. Reactions of
Hydroxylamine with Metal Porphyrins. Inorg. Chem. 1997, 36, 3113.
24) Scheidt, W. R.; Hatano, K.; Rupprecht, G. A.; Piciulo, P. L.
Nitrosylmetalloporphyrins. 5. Molecular stereochemistry of nitrosyl-
5,10,15,20-tetratolylporphinato)manganese(II) and nitrosyl(4-
(
(
methylpiperidine)(5,10,15,20-tetraphenylporphinato)manganese(II).
Inorg. Chem. 1979, 18, 292.
(
25) Zhang, R.; Horner, J. H.; Newcomb, M. Laser Flash Photolysis
Generation and Kinetic Studies of Porphyrin-Manganese-Oxo
Intermediates. Rate Constants for Oxidations Effected by Porphyr-
V
in-Mn -Oxo Species and Apparent Disproportionation Equilibrium
IV
Constants for Porphyrin-Mn -Oxo Species. J. Am. Chem. Soc. 2005,
1
(
27, 6573.
26) Wayland, B. B.; Olson, L. W.; Siddiqui, Z. U. Nitric Oxide
Complexes of Manganese and Chromium Tetraphenylporphyrin. J.
Am. Chem. Soc. 1976, 98, 94.
(
27) (a) Mondal, B.; Saha, S.; Borah, D.; Mazumdar, R.; Mondal, B.
Nitric Oxide Dioxygenase activity of a nitrosyl complex of cobalt(II)
porphyrinate in presence of hydrogen peroxide via putative
peroxynitrite intermediate. Inorg. Chem. 2019, 58, 1234. (b) Kur-
tikyan, T. S.; Hayrapetyan, V. A.; Mehrabyan, M. M.; Ford, P. C. Six-
Coordinate Nitrito and Nitrato Complexes of Manganese Porphyrin.
Inorg. Chem. 2014, 53, 11948. (c) Suslick, K. S.; Watson, R. A.
Photochemical Reduction of Nitrate and Nitrite by Manganese and
Iron Porphyrins. Inorg. Chem. 1991, 30, 912.
(
28) (a) Saha, S.; Gogoi, K.; Mondal, B.; Ghosh, S.; Deka, H.;
Mondal, B. Reaction of a nitrosyl complex of cobalt porphyrin with
hydrogen peroxide: Putative formation of a peroxynitrite intermedi-
ate. Inorg. Chem. 2017, 56, 7781. (b) Richter-Addo, G. B.; Hodge, S.
J.; Yi, G.-B.; Khan, M. A.; Ma, T.; Van Caemelbecke, E.; Guo, N.;
Kadish, K. M. Synthesis, Characterization, and spectroelectrochem-
istry of cobalt porphyrins containing axially bound nitric oxide. Inorg.
Chem. 1996, 35, 6530.
(
29) Groves, J. T.; Stern, M. K. Synthesis, characterization, and
reactivity of oxomanganese(IV) porphyrin complexes. J. Am. Chem.
Soc. 1988, 110, 8628.
(
30) Leto, D. F.; Ingram, R.; Day, V. W.; Jackson, T. A.
Spectroscopic properties and reactivity of a mononuclear
oxomanganese(IV) complex. Chem. Commun. 2013, 49, 5378.
(
31) Parsell, T. H.; Behan, R. K.; Green, M. T.; Hendrich, M. P.;
IV
Borovik, A. S. Preparation and Properties of a Monomeric Mn -Oxo
Complex. J. Am. Chem. Soc. 2006, 128, 8728.
(
32) (a) Reed, C. A.; Kouba, J. K.; Grimes, C. J.; Cheung, S. K.
Manganese(II) and Chromium (II) porphyrin complexes: Synthesis
and Characterization. Inorg. Chem. 1978, 17, 2666. (b) Boucher, L.
Manganese porphyrin complexes. Coord. Chem. Rev. 1972, 7, 289.
(
c) Hoffman, B. M.; Weschler, C. J.; Basolo, F. The dioxygen adduct
of meso-tetraphenylporphyrinmanganese(II), a synthetic oxygen
carrier. J. Am. Chem. Soc. 1976, 98, 5473.
G
DOI: 10.1021/acs.inorgchem.9b02359
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