Electronic tuning of nitric oxide release from manganese nitrosyl complexes by visible light irradiation: Enhancement of nitric oxide release efficiency by the nitro-substituted quinoline ligand

Article abstract of DOI:10.1039/c3dt51719e

Manganese nitrosyl {MnNO}⁶ complexes of general formula [Mn(dpaq^R)(NO)]ClO₄ (1^R), where dpaq ^R denotes a series of pentadentate monoamido ligands, 2-[N,N-bis(pyridin-2-ylmethyl)]-amino-N′-quinolin-8-yl-acetamido with R = OMe, H, Cl and NO₂ at the 5-position of the quinoline moiety, were prepared. The derivatives 1^R were characterized by ¹H NMR, IR and UV-vis spectrometry as well as by single-crystal X-ray crystallography. The N-O bond and the amido C=O bond stretching frequencies, as well as the redox potentials of 1^R derivatives, substantially varied depending on the nature of the substituent group R on the quinoline ring, indicating that the π back-bonding from Mn to NO groups becomes weak as the substituent group R becomes more electron withdrawing. The nitro-substituted derivative 1 ^NO2 is unique among the series; the tail of its absorption bands extends to the NIR region (up to 700 nm), and the apparent NO releasing rate from 1^NO2 by light irradiation at 650 nm was ca. 4-fold higher than the other derivatives.

Full text of DOI:10.1039/c3dt51719e

Dalton
Transactions
View Article Online
View Journal | View Issue
PAPER
Electronic tuning of nitric oxide release from
manganese nitrosyl complexes by visible light
irradiation: enhancement of nitric oxide release
efficiency by the nitro-substituted quinoline
ligand†
Cite this: Dalton Trans., 2014, 43,
2161
Yutaka Hitomi,* Yuji Iwamoto and Masahito Kodera
Manganese nitrosyl {MnNO}6 complexes of general formula [Mn(dpaqR)(NO)]ClO4 (1R), where dpaqR
denotes a series of pentadentate monoamido ligands, 2-[N,N-bis(pyridin-2-ylmethyl)]-amino-N’-quinolin-
8-yl-acetamido with R = OMe, H, Cl and NO2 at the 5-position of the quinoline moiety, were prepared. The
derivatives 1R were characterized by 1H NMR, IR and UV–vis spectrometry as well as by single-crystal X-ray
crystallography. The N–O bond and the amido CvO bond stretching frequencies, as well as the redox
potentials of 1R derivatives, substantially varied depending on the nature of the substituent group R on the
quinoline ring, indicating that the π back-bonding from Mn to NO groups becomes weak as the substituent
group R becomes more electron withdrawing. The nitro-substituted derivative 1NO2 is unique among the
series; the tail of its absorption bands extends to the NIR region (up to 700 nm), and the apparent NO
releasing rate from 1NO2 by light irradiation at 650 nm was ca. 4-fold higher than the other derivatives.
Received 27th June 2013,
Accepted 8th November 2013
DOI: 10.1039/c3dt51719e
www.rsc.org/dalton
effectively release NO by low-intensity light irradiation at long
wavelengths. Metal nitrosyl complexes are promising Photo-
Introduction
Nitric oxide (NO) is well established as a signaling molecule NORM candidates since many of these complexes release NO
that functions in the cardiovascular, nervous, and immune by photo-irradiation. Photosensitizers are often used to con-
systems.1–3 The biological roles of NO not only explain the struct PhotoNORMs that can be activated by light irradiation
action of nitroglycerin, organic nitrates, and sodium nitroprus- at desired wavelengths;11,13 such dye-sensitized PhotoNORMs
+
side, all of which have been used as therapeutic agents for a include trans-Cr(cyclam)(ONO)2 complexes having pendant
long time, but also lead to development of various NO-releas- aromatic chromophores (cyclam = 1,4,8,11-tetraazacyclotetra-
ing molecules (NORMs), because they are expected to be useful decane),16 electrostatic assemblies between anionic semicon-
+ 17
tools for biological research. In addition, NORMs—such as ductor quantum dots and cationic trans-Cr(cyclam)(ONO)2 ,
organic nitrites and nitrates, S-nitroso compounds, and dye-attached iron/sulfur/nitrosyl clusters Fe2(μ-RS)2(NO)4,18,19
diazeniumdiolates4–7 and metal nitrosyl complexes8—are and ruthenium nitrosyl complexes having NIR dyes as
expected to be potential therapeutic agents. In the past ligands.20,21 Appropriate ligand designs for metal nitrosyls are
decade, photoactive NORMs (PhotoNORMs)9 have received a powerful alternative approach.22,23 For example, Mascharak’s
much attention because they can deliver NO to biological group reported that
a diamagnetic manganese nitrosyl
targets in a temporally and spatially controlled manner.10–15 complex represented as {MnNO}6 in the Enemark–Feltham
PhotoNORMs are stable in aqueous solutions in the dark and notation,24 [Mn(PaPy3)(NO)]ClO4 (PaPy3 = N,N-bis(2-pyridyl-
only release NO upon photoirradiation at an appropriate wave- methyl)amine-N-ethyl-2-pyridine-2-carboxamido),
has
an
length. To minimize tissue damage caused by photoirradia- absorption band at around 650 nm and releases NO in
tion, it is desirable to produce PhotoNORMs that can aqueous media when exposed to visible light of low intensity
(ϕ = 0.55 and λirr = 532 nm).25,26 Recent theoretical studies
have provided insight into the transitions that lead to NO
release by photo-irradiation.27–29 Notably, [Mn(PaPy3)(NO)]-
Department of Molecular Chemistry and Biochemistry, Faculty of Science and
Engineering, Doshisha University, 1–3 Tatara Miyakodani, Kyotanabe, Kyoto
ClO4 has been successfully applied for activating soluble gua-
610–0321, Japan. E-mail: yhitomi@doshisha.ac.jp
†Electronic supplementary information (ESI) available: Crystallographic data,
nylate cyclase or for eradicating bacteria.30–33 More impor-
tantly, the sensitivity of the {MnNO}6 complex against low-
and additional tables and figures. CCDC 947309–947312. For ESI and crystallo-
energy light can be further enhanced by replacing a pyridine
graphic data in CIF or other electronic format see DOI: 10.1039/c3dt51719e
This journal is © The Royal Society of Chemistry 2014
Dalton Trans., 2014, 43, 2161–2167 | 2161

View Article Online
Paper
Dalton Transactions
Et3N in CH3CN, obtained as white solids and found to be air
stable in the solid state. Respective nitrosyl complexes 1R were
synthesized by bubbling purified NO gas in the [Mn(II)(dpaqR)]-
ClO4 solution in CH3CN under anaerobic conditions. In most
cases, the colour of the reaction mixture changed from yellow
to brown within 30 s during NO bubbling. All nitrosyl com-
plexes 1R were obtained as brown solids that were air stable in
the dark. All 1R complexes were soluble in CH3CN and H2O;
however, they were not soluble in less polar solvents, such as
hexane or CH2Cl2.
Crystallography
Crystals of 1R suitable for X-ray diffraction were reproducibly
grown by vapour diffusion of ethyl acetate into the CH3CN
solution of 1R derivatives at room temperature (Fig. 1). The
coordination structures of 1R derivatives resemble the reported
structure of [Mn(PaPy3)(NO)]ClO4 (2)26 and [Mn(PaPy2Q)(NO)]-
ClO4 (3),23 i.e., the metal centres are in a distorted octahedral
geometry, and the amido nitrogen is located trans to NO. The
Mn–N–O angles are nearly linear as observed for {MnNO}6
complexes.23,26,36–38 The N–O and Mn–NO bonds range from
1.02 to 1.14 Å and from 1.63 to 1.74 Å, respectively, which is
comparable to those observed for 2 and 3 (Table 1).23,26
However, the metric parameters of the {MnNO}6 unit in 1R
compounds do not show a clear correlation that is expected by
the substituted groups on the ligand, which may be caused by
the disorder of the NO ligand. On the other hand, the Mn–N4
(amido) bond distance increases, and the CvO bond distance
gradually decreases as the substituent becomes more electron
withdrawing (Table 1), showing that the substitution groups
modulate the coordination strength of the amido ligand as
expected.
Chart 1 Chemical structures of supporting ligands.
with a quinoline ring.23 We focused on the latter ligand design
approach owing to its simplicity and ability to synthesize
relatively small PhotoNORMs compared to dye-sensitized
PhotoNORMs.
In this study, we aimed to clarify how the supporting ligand
of {MnNO}6 complexes changes the electronic structures and
consequently the NO release efficiency upon photo-irradiation.
Herein, we have used a series of pentadentate monoamido
ligands, where dpaqR denotes four pentadentate monoamido
ligands, 2-[N,N-bis(pyridin-2-ylmethyl)]-amino-N′-quinolin-8-yl-
acetamido with R = OMe, H, Cl and NO2 at the 5-position of
the quinoline moiety (Chart 1), which we recently prepared in
our laboratory,34,35 to construct a series of {MnNO}6 com-
plexes. We expected that the substituted group on the quino-
line ligand should modulate the coordination strength of the
amido ligand, and that the stronger amido coordination
should donate more electron density to the Mn center, increas-
ing the π back-bonding from the Mn to the NO ligand. Herein,
we present the syntheses and structures of a series of {MnNO}6
complexes, [Mn(dpaqR)(NO)]ClO4 (1R, R = OMe, H, Cl and
NO2), and their NO-release efficiency upon photoirradiation at
specific wavelengths.
NMR spectra
1H NMR spectra of 1R were measured in CD3CN, and all
signals appear in the range of 4.0–9.4 ppm (Fig. S1†), as
observed for the diamagnetic {MnNO}6 complexes 2 and 3.23,26
Peak assignments are listed in Table S3.† A singlet at ca.
4 ppm was attributed to the CH2 moiety next to the carbox-
Results and discussion
Syntheses
amido ligand. An AB quartet at ca. 4.4 and ca. 4.6 ppm (JAB
=
15.5 Hz) was ascribed to CH2 moieties of two pyridylmethyl
Mn(II) complexes [Mn(II)(dpaqR)]ClO4 were synthesized by arms. These 1H NMR signals are in agreement with the Cs sym-
reacting Mn(ClO4)2 with H-dpaqR ligand in the presence of metry, suggesting that the crystal structure is retained in the
Fig. 1 Ortep representation of the cation of 1R derivatives at 50% probability level. H atoms are omitted for clarity.
2162 | Dalton Trans., 2014, 43, 2161–2167
This journal is © The Royal Society of Chemistry 2014

View Article Online
Dalton Transactions
Paper
Table 1 Selected angle, bond lengths, and stretching frequencies of {MnNO}6 complexes
Mn–N–O/°
N–O/Å
Mn–NO/Å
Mn–Namido/Å
CvO/Å
νNO/cm−1
νCO/cm−1
1OMe
1H
176.7(8)
171(2)
171.3(3)
175.8(6)
171.91(13)
171.5(8)
1.015(7)
1.022(16)
1.044(4)
1.136(7)
1.1918(18)
1.237(18)
1.742(8)
1.635(12)
1.713(4)
1.660(5)
1.6601(14)
1.678(3)
1.923(7)
1.998(9)
1.941(3)
1.957(5)
1.9551(14)
1.956(3)
1.247(9)
1.225(15)
1.240(4)
1.217(7)
1.244(2)
1.243(4)
1737
1739
1743
1744
1745
1725
1602
1612
1624
1636
1627
1634
1Cl
1NO2
2a
3b
a Data from ref. 26. b Data from ref. 23.
1
solution. H NMR spectra of all the 1R derivatives were nearly
identical, except for protons at 4- and 6-positions of the quino-
line ring. The proton signals shifted by +0.88 and +0.95 ppm
from R = H to R = NO2; the shifts of the other signals were
within 0.10 ppm (Table S3†).
IR spectra
In the solid state IR spectra of 1R compounds, two intense
vibration bands were observed (Fig. S2†). One signal appeared
in the range of 1737–1744 cm−1, while the other signal was
found in the range of 1602–1636 cm−1 (Table 1). The band at a
higher wavenumber arises from the N–O vibration, while the
band at a lower wavenumber corresponds to the CvO stretch-
ing vibration of the carboxamido moiety. The N–O vibration
values are similar to the N–O stretch for 2 and 3. Both CvO
and N–O bands shifted to a higher energy as the substituent
became electron withdrawing. The observed changes for the
CvO vibration are consistent with those for the CvO bond
distance in their crystal structures. The changes for CvO and
N–O bands show a clear linear correlation (Fig. 2). These
results suggest that, as the substituent group became more
electron withdrawing, the strength of carboxamido ligation
decreased together with the π back-bonding from the Mn to
NO ligand.
Fig. 3 Hammett plot for the redox potential of 1R derivatives.
state decreases in the order of R = NO2 > Cl > H > OMe. The
redox potentials follow a linear relationship against the
Hammett substituent constants with ρ-values of 131
6
(Fig. 3), which clearly illustrates the substituent effect on the
{MnNO}6 unit.
Absorption spectra
The solutions of ligands H-dpaqR and their Mn(II) complexes
[Mn(II)dpaqR]ClO4 in CH3CN show two absorption bands at
around 250 and 350 nm (Fig. 4 and Table S5†). These bands
should be assignable to π–π* transitions of quinoline rings.
The bands of [Mn(II)dpaqR]ClO4 appear at a lower energy than
those of the respective ligands, owing to the metalation of the
carboxamide moiety of H-dpaqR. The energy of the bands at
around 350 nm decreases in the order of R = H > Cl > OMe >
NO2 in both series of H-dpaqR and [Mn(II)dpaqR]ClO4.
Especially, large bathochromic shifts were observed for nitro-
substituent derivatives, H-dpaqNO2 and [Mn(II)dpaqNO2]ClO4,
which should be caused by stabilization of quinoline π* orbi-
tals because of the nitro group.
Electrochemistry
Compounds 1R exhibited a quasi-reversible {MnNO}5/{MnNO}6
couple in the range of 0.49–0.63 V versus Fc+/Fc in CH3CN
(Fig. S3†). The redox potential of 2 was 0.50 V versus Fc+/Fc,
indicating that dpaqR ligands with R = NO2, Cl and H are
weaker donor ligands than PaPy3. The stability of the {MnNO}6
While the solutions of [Mn(II)dpaqR]ClO4 in CH3CN are col-
ourless for R = H and Cl, pale yellow for R = OMe and yellow
for R = NO2, nitrosyl complexes 1R in CH3CN are yellow. The
absorption spectra of 1OMe, 1H and 1Cl in CH3CN have similar
features, showing two absorption bands ranging from 357 to
475 nm and a very weak broad band at around 600 nm (Fig. 5).
On the other hand, 1NO2 showed an intense band at 423 nm, a
weak band at 513 nm and a weak shoulder band at 650 nm
(ε = 493 M−1 cm−1). Thus, the tail of absorption bands of 1NO2
extends to the NIR region (up to 700 nm), which should corre-
late to the bathochromic shifts observed for H-dpaqNO2 and
[Mn(II)dpaqNO2]ClO4. The absorption spectra of 1R derivatives
Fig. 2 Correlation graph of νN–O and νCvO frequencies for 1R
derivatives.
This journal is © The Royal Society of Chemistry 2014
Dalton Trans., 2014, 43, 2161–2167 | 2163

View Article Online
Paper
Dalton Transactions
Fig. 6 Electronic spectral change of a solution of 1NO2 in MES buffer
(pH 7.2, 5% DMSO) at 20 °C under irradiation at 650 nm. The arrow indi-
cates a decrease in band intensities as the reaction proceeds. Inset: time
profile of the absorbance at 521 nm.
the decomposition of 1R was verified by assay using reduced
myoglobin (Fig. S5†). We further investigated the dependence
of the conversion rate on irradiation wavelength. The conver-
sion of 1R, together with 2 as a reference, was spectrophotome-
trically monitored in MES buffer (pH 7.2, 5% DMSO) at 20 °C
under irradiation at 460, 530 and 650 nm. The light at the
wavelength was kept at the same intensity (300 mW m−2). The
Fig. 4 Electric absorption spectra of H-dpaqR (A) and [Mn(dpaqR)]ClO4
(B) in CH3CN at 20 °C. R: OMe, green; H, blue; Cl, purple and NO2, red.
absorption bands characteristic to 1R and 2 (457 nm for 1OMe
,
461 nm for 1H, 475 nm for 1Cl, 521 nm for 1NO2 and 450 nm
for 2) disappeared within 30 min under light irradiation (Fig. 6
and S5†). The decay rates were dependent on the irradiation
wavelength; the decomposition of 1R became slower in the
order of 1OMe ≈ 1H > 1Cl > 1NO2 under light irradiation at
460 nm, while the order was reversed in the case of irradiation
at 530 or 650 nm, 1OMe < 1H < 1Cl < 1NO2. Notably, the decay of
1NO2 by light irradiation at 650 nm was ca. 4-fold faster than
the other derivatives.
The quantum yields (QYs) of NO release from 1R upon light
irradiation at 460 nm were almost indistinguishable, falling
between 0.58 and 0.66 (Table 2). Although the QYs at 530 and
650 nm for 1Cl and 1NO2 were slightly higher than those for
1OMe and 1H, the small difference in the QYs cannot account
for the observed 4-fold faster NO-release from 1NO2 under light
irradiation at 650 nm. The similar QYs for 1R series indicate
that there is no significant difference in the inherent reactivity
of the excited states formed from 1R derivatives. The faster NO
release from 1NO2 under light irradiation at 650 nm should be
mainly attributed to the higher absorption coefficients of 1NO2
at 650 nm (Table 2), because the rate of a photochemical
process is proportional to the intensity of the light absorbed
and to the quantum yield.39
Fig. 5 Electric absorption spectra of 1R (A) in CH3CN at 20 °C. R: OMe,
green; H, blue; Cl, purple and NO2, red. Panel B shows a magnification
in the range of 400 to 800 nm. Vertical dotted lines show the wave-
lengths of light irradiation (460, 530 and 650 nm).
in MES buffer (pH 7.2) were almost identical to those in MeCN
(Fig. S4 and Table S5†).
Conclusions
Photoinduced NO release
Depending on the electronic nature of the substituent group of
The nitrosyl complexes 1R are stable in aqueous media even at the quinoline ring, the NO vibration frequencies of 1R and the
37 °C in the dark over 10 days. Under UV light irradiation, redox potentials of {MnNO}5/{MnNO}6 couple vary substan-
however, these complexes rapidly transformed into the corres- tially. For example, compound 1NO2 shows the highest NO fre-
ponding Mn(II) complexes. Formation of NO concomitant with quency and redox potential, suggesting weak π back-bonding
2164 | Dalton Trans., 2014, 43, 2161–2167
This journal is © The Royal Society of Chemistry 2014

View Article Online
Dalton Transactions
Paper
Table 2 Molar extinction coefficients and quantum yields for NO release at specific wavelengths
ε (mM−1 cm−1
)
ϕ (mol einstein−1
)
Complex
460 nm
530 nm
650 nm
460 nm
530 nm
650 nm
1OMe
1H
4.20
3.11
2.69
1.77
2.04
0.370
0.363
0.707
1.56
0.111
0.123
0.113
0.493
0.220
0.58 0.04
0.61 0.03
0.66 0.04
0.61 0.05
0.71 0.04
0.47 0.01
0.51 0.01
0.66 0.02
0.63 0.01
0.59 0.02
0.49 0.01
0.47 0.01
0.73 0.01
0.78 0.01
0.39 0.01
1Cl
1NO2
2
0.113
from the Mn to the NO ligand in 1NO2. Therefore, we first presented with respect to the Fc+/Fc couple at the same scan
expected that 1NO2 should be the most active PhotoNORM rate (20 mV s−1).
among 1R. However, the reactivity order of NO release from 1R
was highly dependent on the irradiation wavelength, but was
independent of the electronic nature of the substituent
Synthesis of the manganese(II) complexes
groups. Thus, the rates of photoinduced NO release from 1R
Caution! Perchlorate salts of metal complexes are potentially
are exclusively determined by the absorption coefficient, at
explosive. Only small quantities of the material should be pre-
which wavelength light is absorbed.
pared, and the samples should be handled with care.
The nitro-substituted derivative 1NO2 exhibited absorption
A solution of H-dpaqR (0.26 mmol) in CH3CN (2 mL) con-
bands extending up to 700 nm, which should be caused by the
taining Et3N (40 μL, 0.29 mmol) was added to a solution of Mn-
stabilization of the quinoline π* orbital by introduction of the
(ClO4)2·6H2O (0.11 g, 0.31 mmol) in CH3CN (0.5 mL) at room
nitro group on the quinoline ring. Because of this absorption
temperature. The mixture was stirred for 2 h. The precipitate
band, 1NO2 can release NO by photo-irradiation at 650 nm with
was collected, washed with diethyl ether, and dried in vacuo.
a ca. 4-fold higher rate than the other derivatives. Our results
[Mn(dpaqOMe)]ClO4. Yellow solid. Yield: 55%. Anal. calcd
suggest that the stabilization of π* orbitals of the aromatic ligand
for [Mn(dpaqOMe)](ClO4)(H2O)0.5: C, 50.06; H, 4.03; N, 12.16.
to Mn is a promising strategy to design {MnNO}6 PhotoNORMs
Found: C, 50.22; H, 4.00; N, 12.35. Selected IR frequencies
that can release NO with even higher efficiency by light
(cm−1, FT-ATR): 1549 (CO). Electronic absorption spectrum
irradiation at long wavelengths.
in CH3CN (nm (M−1 cm−1)): 405 (3320), 346 (2330), 264
(33 200). Electronic absorption spectrum in MES buffer (pH
7.2, 5% DMSO) (nm (M−1 cm−1)): 334 (4270), 248 (29 200).
ESI-MS, positive mode: m/z 467.19 {Mn(dpaqOMe)}+.
Experimental section
General
[Mn(dpaqH)]ClO4. Pale yellow solid. Yield: 90%. Anal. calcd
for [Mn(dpaqH)](ClO4)(H2O)0.8: C, 50.11; H, 3.95; N, 12.70.
The reagents and the solvents used in this study, except the Found: C, 50.19; H, 3.81; N, 12.74. Selected IR frequencies
ligands and the manganese complexes, were commercial pro- (cm−1, FT-ATR): 1541 (CO). Electronic absorption spectrum
ducts of the highest available purity and were further purified in CH3CN (nm (M−1 cm−1)): 375 (4500), 262 (37 100). Elec-
by standard methods, if necessary. Ligand H-dpaqH was pre- tronic absorption spectrum in MES buffer (pH 7.2, 5% DMSO)
pared according to the reported procedure.34 The other (nm (M−1 cm−1)): 309 (5300), 241 (23 800). ESI-MS, positive
ligands H-dpaqR (R = OMe, Cl and NO2) were synthesized mode: m/z 437.08 {Mn(dpaqH)}+.
through procedures similar to that for H-dpaqH. Details will be
[Mn(dpaqCl)]ClO4. Pale yellow solid. Yield: 84%. Anal. calcd
reported elsewhere.35 [Mn(PaPy3)(NO)]ClO4 (2) was prepared for [Mn(dpaqCl)](ClO4)(H2O)0.5: C, 47.61; H, 12.07; N, 3.47.
following the procedure reported by Ghosh et al.26 Room temp- Found: C, 47.76; H, 11.89; N, 3.48. Selected IR frequencies
erature 1H NMR spectra were recorded using a JMN-A 500 (cm−1, FT-ATR): 1537 (CO). Electronic absorption spectrum
spectrometer at 500 MHz frequency. Infrared spectra (IR) were in CH3CN (nm (M−1 cm−1)): 388 (5330), 264 (25 900). Elec-
recorded on a Shimadzu IRAffinity-1 spectrometer with a Pike tronic absorption spectrum in MES buffer (pH 7.2, 5% DMSO)
MIRacle10 ATR system (ZnSe). Electrospray ionization mass (nm (M−1 cm−1)): 325 (5280), 244 (25 300). ESI-MS, positive
spectroscopy was performed on a JEOL JMS-T100CS spectro- mode: m/z 471.12 {Mn(dpaqCl)}+.
meter. Electronic spectra of complexes were recorded using an
[Mn(dpaqNO2)]ClO4. Orange solid. Yield: 93%. Anal. calcd
Agilent 8543 UV–vis spectrometer. Cyclic voltammograms were for [Mn(dpaqNO2)](ClO4)(H2O)0.5: C, 46.76; H, 3.41; N, 14.22.
recorded by a Bioanalytical Systems (BAS) model CV-50W Found: C, 47.03; H, 3.26; N, 13.92. Selected IR frequencies
instrument using dry and degassed CH3CN solutions with (cm−1, FT-ATR): 1533 (CO). Electronic absorption spectrum
0.1 M NBu4ClO4 and 1 mM complexes. The electrodes were as in CH3CN (nm (M−1 cm−1)): 428 (19 100), 322 (3990), 262
follows: Pt (working), Pt wire (auxiliary), and Ag/AgCl in (22 900). Electronic absorption spectrum in MES buffer (pH
CH3CN (reference). At the end of each measurement, the 7.2, 5% DMSO) (nm (M−1 cm−1)): 380 (10 100), 238 (12 000).
potentials were internally calibrated using Fc+/Fc couple, and ESI-MS, positive mode: m/z 482.15 {Mn(dpaqNO2)}+.
This journal is © The Royal Society of Chemistry 2014
Dalton Trans., 2014, 43, 2161–2167 | 2165

View Article Online
Paper
Dalton Transactions
Synthesis of {MnNO}6 complexes
intensities were recorded on a Rigaku R-AXIS RAPID IP X-ray
diffractometer using graphite-monochromatized Cu-Kα radi-
ation (λ = 1.54187 Å), operating at 133 K. The structures have
been solved by direct methods using SIR200440 and were
refined using the Shelx-97 program package.41 The hydrogen
atoms residing in the carbon atoms were located geometri-
cally. The oxygen atoms of perchlorate anion were judged to be
All procedures were performed in the dark. A solution of [Mn-
(dpaqR)]ClO4 (0.093 mmol) in CH3CN (1.5 mL) was degassed
and bubbled with purified NO gas (50 mL × 3) with vigorous
stirring. Brown precipitates were filtered, washed with Et2O,
and dried under vacuum.
[Mn(dpaqOMe)(NO)]ClO4. Dark green solid. Yield: 65%.
Anal. calcd for [Mn(NO)(dpaqOMe)](ClO4)(CH3CN)0.5: C, 48.64;
disordered over two sites with 50% population each for 1OMe
,
1
and over three sites (30 : 30 : 40) for 1Cl. The perchlorate within
1H was judged located at two sites and each perchlorate ion
has an occupation factor of 0.5. In the refinement, the Cl–O
distances were restrained to 1.42(2) Å. The O⋯O distances
within each perchlorate ion were restrained to be equal and to
have same isotropic displacement parameter. Owing to the
two-site disorder of the perchlorate anion within 1H, the NO
moiety of 1H showed a large disorder, resulting in the larger
R-value. All non-hydrogen atoms were refined anisotropically.
Important crystallographic parameters and selected bond dis-
tances/angles are listed in Tables S1 and S2.†
H, 3.84; N, 14.75. Found: C, 48.79; H, 3.84; N, 14.75. H NMR
(500 MHz, CD3CN): 9.27 (dd, 1H), 8.90 (d, 1H), 8.63 (dd, 1H),
7.82 (t, 2H), 7.63 (dd, 1H), 7.47 (d, 2H), 7.15 (d, 1H), 7.02 (t,
2H), 6.33 (d, 2H), 4.55 (d, 2H), 4.35 (d, 2H), 4.03 (s, 3H), 3.95
(s, 2H). Selected IR frequencies (cm−1, FT-ATR): 1737 (NO),
1602 (CO). Electronic absorption spectrum in CH3CN (nm
(M−1 cm−1)): 459 (5090), 356 (2450), 265 (25 300). Electronic
absorption spectrum in MES buffer (pH 7.2) (nm (M−1 cm−1)):
457 (4230), 398 (3830).
[Mn(dpaqH)(NO)]ClO4. Brown solid. Yield: 75%. Anal. calcd
for [Mn(NO)(dpaqH)](ClO4)(H2O): C, 47.23; H, 3.79; N, 14.37.
Found: C, 47.18; H, 3.55; N, 14.23. 1H NMR (500 MHz,
CD3CN): 9.25 (d, 1H), 8.97 (d, 1H), 8.39 (d, 1H), 7.83 (t, 2H),
7.72 (t, 1H), 7.65 (dd, 1H), 7.63 (d, 1H), 7.48 (d, 2H), 7.02 (t,
2H), 6.31 (d, 2H), 4.57 (d, 2H), 4.37 (d, 2H), 4.00 (s, 2H).
Selected IR frequencies (cm−1, FT-ATR): 1739 (NO), 1612 (CO).
Electronic absorption spectrum in CH3CN (nm (M−1
cm−1)): 459 (3940), 382 (4160), 259 (25 900). Electronic
absorption spectrum in MES buffer (pH 7.2) (nm (M−1 cm−1)):
461 (3120), 357 (3910).
Kinetic measurements
For kinetic analysis of the decomposition of 1R and 2 as a
reference in MES buffer (pH 7.2, 5% DMSO) at 20 °C, the
decrease in absorbance at 457 nm for 1OMe, 461 nm for 1H,
475 nm for 1Cl, 521 nm for 1NO2 and 450 nm for 2, which are
characteristic of {MnNO}6 species, was monitored as a func-
tion of time under irradiation. Solutions of 1R or 2 were irra-
diated from the top of the cell using a 300 W xenon lamp
(Asahi Spectra Co. Ltd) through band-pass filters transmitting
λ = 460 nm (FWHW: 5 nm), 530 nm (FWHW: 5 nm), and
650 nm (FWHW: 6 nm). The intensity was adjusted at 300 mW
m−2 measured by photoradiometer HD 2303.0 equipped with
an irradiance measurement probe LP471RAD (Delta OHM,
S.r.L). The rate constants were obtained from nonlinear least-
squares fits of the experimental data to an exponential
function.
[Mn(dpaqCl)(NO)]ClO4. Brown solid. Yield: 60%. Anal. calcd
for [Mn(NO)(dpaqCl)](ClO4)(H2O)0.75: C, 45.25; H, 3.10; N,
1
13.31. Found: C, 44.93; H, 3.36; N, 13.67. H NMR (500 MHz,
CD3CN): 9.33 (d, 1H), 8.92 (d, 1H), 8.63 (d, 1H), 7.84 (t, 2H),
7.77 (m, 2H), 7.48 (d, 2H), 7.03 (t, 2H), 6.35 (d, 2H), 4.56 (d,
2H), 4.36 (d, 2H), 3.99 (s, 2H). Selected IR frequencies (cm−1
,
FT-ATR): 1743 (NO), 1624 (CO). Electronic absorption spec-
trum in CH3CN (nm (M−1 cm−1)): 474 (3760), 398 (5140), 260
(26 900). Electronic absorption spectrum in MES buffer
(pH 7.2) (nm (M−1 cm−1)): 475 (2960), 375 (4560).
Quantum yield measurement
Chemical actinometry was used to obtain the photon flux via
photolysis of Reinecke salt, K[Cr(NH3)2(NCS)4], solutions.42
The solutions (3 mL) of Reinecke salt in H2O or {MnNO}6 com-
plexes 1R and 2 in MES buffer (pH 7.2, 5% DMSO) in a 1 cm
quartz cuvette were irradiated from the top of the cell using a
300 W xenon lamp (Asahi Spectra Co. Ltd) through a band-
pass filter transmitting λ = 460 nm (FWHW: 5 nm). The inten-
sity was adjusted at 3.1 mW m−2. UV–vis spectra of 1R and 2 in
MES buffer (pH 7.2, 5% DMSO) were taken after irradiation for
5000 s, and the decomposed fraction was calculated using
[Mn(dpaqNO2)(NO)]ClO4. Dark drown solid. Yield: 75%.
Anal. calcd for [Mn(NO)(dpaqNO2)](ClO4)(diethyl ether)0.25: C,
1
45.73; H, 3.44; N, 15.55. Found: C, 45.60; H, 3.35; N, 15.64. H
NMR (500 MHz, CD3CN): 9.39 (d, 1H), 9.27 (d, 1H), 8.96 (d,
1H), 8.67 (d, 1H), 7.85 (m, 3H), 7.46 (d, 2H), 7.05 (t, 2H), 6.41
(d, 2H), 4.59 (d, 2H), 4.38 (d, 2H), 4.05 (s, 2H). Selected IR fre-
quencies (cm−1, FT-ATR): 1744 (NO), 1636 (CO). Electronic
absorption spectrum in CH3CN (nm (M−1 cm−1)): 513 (2070),
423 (14 500), 314 (5870), 264 (20 600). Electronic absorption
spectrum in MES buffer (pH 7.2) (nm (M−1 cm−1)): 523 (1570),
392 (10 300).
changes in the absorption spectrum at 457 nm for 1OMe
,
461 nm for 1H, 475 nm for 1Cl, 521 nm for 1NO2 and 450 nm
for 2: 0.146 μmol for 1OMe, 0.157 μmol for 1H, 0.169 μmol for
1Cl, 0.156 μmol for 1NO2 and 0.182 μmol for 2, which corres-
X-ray crystallography
Brown crystals of manganese nitrosyl complexes were obtained pond to less than 10% of the initial complexes. Then, the QYs
by vapour diffusion of acetonitrile into the ethyl acetate solu- of 1R derivatives were estimated from the decomposition frac-
tion of the complex. X-ray quality single crystals were mounted tion of Reinecke salt (0.0792 μmol) under identical conditions
on tips made from polymer films (MicroMount). The using the reported Reinecke salt’s quantum yield with
2166 | Dalton Trans., 2014, 43, 2161–2167
This journal is © The Royal Society of Chemistry 2014

View Article Online
Dalton Transactions
Paper
ϕ = 0.31.42 The QYs at 530 and 650 nm were estimated based 18 S. R. Wecksler, A. Mikhailovsky, D. Korystov, F. Buller,
on the QYs at 460 nm and the initial reaction rate constants
R. Kannan, L. S. Tan and P. C. Ford, Inorg. Chem., 2007, 46,
395–402.
measured for 1R derivatives under light irradiation at 460 nm
using the following equation: QY = QY460 nm × (kint_460 nm/kint
× (Iabs/Iabs_460 nm), where kint and Iabs denote the initial reaction
)
19 S. R. Wecksler, A. Mikhailovsky, D. Korystov and P. C. Ford,
J. Am. Chem. Soc., 2006, 128, 3831–3837.
rate constant and the absorbed light intensity, respectively 20 M. J. Rose and P. K. Mascharak, Inorg. Chem., 2009, 48,
(Table S6†).
6904–6917.
21 M. J. Rose, N. L. Fry, R. Marlow, L. Hinck and
P. K. Mascharak, J. Am. Chem. Soc., 2008, 130, 8834–8846.
22 C. G. Hoffman-Luca, A. A. Eroy-Reveles, J. Alvarenga and
P. K. Mascharak, Inorg. Chem., 2009, 48, 9104–9111.
Acknowledgements
We are grateful to the late Suemoto Naoya for his preliminary 23 A. A. Eroy-Reveles, Y. Leung, C. M. Beavers, M. M. Olmstead
contribution to this study. We thank Dr Shuhei Furukawa for and P. K. Mascharak, J. Am. Chem. Soc., 2008, 130, 4447–4458.
the kind use of his NOx analyzer and acknowledge useful dis- 24 J. H. Enemark and R. D. Feltham, Coord. Chem. Rev., 1974,
cussion with Dr Shuhei Furukawa and Dr Stéphane Diring. 13.
This work was supported by Grant-in-Aids for Scientific 25 A. A. Eroy-Reveles, Y. Leung and P. K. Mascharak, J. Am.
Research (No. 24550197 and 21350037) from the Ministry of
Education, Science, Sports, and Culture of Japan.
Chem. Soc., 2006, 128, 7166–7167.
26 K. Ghosh, A. A. Eroy-Reveles, B. Avila, T. R. Holman,
M. M. Olmstead and P. K. Mascharak, Inorg. Chem., 2004,
43, 2988–2997.
27 W. Zheng, S. Wu, S. Zhao, Y. Geng, J. Jin, Z. Su and Q. Fu,
Inorg. Chem., 2012, 51, 3972–3980.
Notes and references
1 L. J. Ignarro, Nitric Oxide: Biology and Pathobiology, Aca- 28 N. L. Fry and P. K. Mascharak, Dalton Trans., 2012, 41,
demic Press, San Diego, 2000. 4726–4735.
2 S. Kalsner, Nitric Oxide Free Radicals in Peripheral Neuro- 29 A. C. Merkle, N. L. Fry, P. K. Mascharak and N. Lehnert,
transmission, Birkhauser, Boston, 2000. Inorg. Chem., 2011, 50, 12192–12203.
3 G. Y. Ko and F. C. Fang, Nitric Oxide and Infection, Kluwer 30 B. J. Heilman, J. St John, S. R. Oliver and P. K. Mascharak,
Academic/Plenum Publishers, New York, 1999. J. Am. Chem. Soc., 2012, 134, 11573–11582.
4 P. G. Wang, M. Xian, X. Tang, X. Wu, Z. Wen, T. Cai and 31 B. J. Heilman, G. M. Halpenny and P. K. Mascharak,
A. J. Janczuk, Chem. Rev., 2002, 102, 1091–1134. J. Biomed. Mater. Res. B Appl. Biomater., 2011, 99, 328–337.
5 J. A. Hrabie and L. K. Keefer, Chem. Rev., 2002, 102, 1135– 32 G. M. Halpenny, K. R. Gandhi and P. K. Mascharak, ACS
1154.
Med. Chem. Lett., 2010, 1, 180–183.
6 G. R. Thatcher, Curr. Top. Med. Chem., 2005, 5, 597–601.
7 H. H. Al-Sa’doni and A. Ferro, Curr. Med. Chem., 2004, 11,
2679–2690.
33 M. Madhani, A. K. Patra, T. W. Miller, A. A. Eroy-Reveles,
A. J. Hobbs, J. M. Fukuto and P. K. Mascharak, J. Med.
Chem., 2006, 49, 7325–7330.
8 A. R. Butler and I. L. Megson, Chem. Rev., 2002, 102, 1155– 34 Y. Hitomi, K. Arakawa, T. Funabiki and M. Kodera, Angew.
1166. Chem., Int. Ed., 2012, 51.
9 A. Ostrowski, Abstracts of Papers, 244th ACS National 35 Y. Hitomi, K. Arakawa and M. Kodera, Chem.–Eur. J., 2013,
Meeting & Exposition, Philadelphia, PA, United States, August
19–23, 2012, 2012, IAC-14.
10 A. D. Ostrowski and P. C. Ford, Dalton Trans., 2009, 10660–
10669.
19, 14697–14701.
36 D. J. Cooper, M. D. Ravenscroft, D. A. Stotter and
J. J. Trotter, J. Chem. Res., Miniprint, 1979, 3359.
37 W. R. Scheidt, K. Hatano, G. A. Rupprecht and P. L. Piciulo,
Inorg. Chem., 1979, 18, 292–299.
11 P. C. Ford, Acc. Chem. Res., 2008, 41, 190–200.
12 M. J. Rose and P. K. Mascharak, Curr. Opin. Chem. Biol., 38 P. L. Piciulo, G. Rupprecht and W. R. Scheidt, J. Am. Chem.
2008, 12, 238–244. Soc., 1974, 96, 5293–5295.
13 N. L. Fry and P. K. Mascharak, Acc. Chem. Res., 2011, 44, 39 J. V. Garcia, F. Zhang and P. C. Ford, Philos. Trans. R. Soc. A,
289–298. 2013, 317, 20120129.
14 M. J. Rose and P. K. Mascharak, Coord. Chem. Rev., 2008, 40 R. C. M. C. Burla, M. Camalli, B. Carrozzini,
252, 2093–2114.
G. L. Cascarano, L. D. Caro, C. Giacovazzo, G. Polidori and
R. J. Spagna, Appl. Crystallogr., 2005, 381–388.
41 G. M. Sheldrick, SHELX97: Programs for the Solution and
Refinement of Crystal Structures, Univ. of Göttingen, Göttin-
gen, 1997, Univ. of Göttingen, Göttingen, 1997.
15 E. Tfouni, M. Krieger, B. R. McGarvey and D. W. Franco,
Coord. Chem. Rev., 2003, 236, 57–69.
16 F. Derosa, X. Bu and P. C. Ford, Inorg. Chem., 2005, 44,
4157–4165.
17 D. Neuman, A. D. Ostrowski, R. O. Absalonson, 42 M. Montalti, A. Credi, L. Prodi and M. T. Gandolfi, Hand-
G. F. Strouse and P. C. Ford, J. Am. Chem. Soc., 2007, 129,
4146–4147.
book of Photochemistry, CRC Press, Boca Raton, 3rd edn,
2006.
This journal is © The Royal Society of Chemistry 2014
Dalton Trans., 2014, 43, 2161–2167 | 2167