Trans-dinitrosyl-substituted hexamolybdate and study of its controllable no release

Article abstract of DOI:10.1002/ejic.201201144

On the basis of the well-developed N,N′-dicyclohexylcarbodiimide (DCC) imidoylization strategy, the novel trans-dinitrosyl-substituted polyoxometalate (POM) (NBu₄)₄[Mo₆O ₁₇(≡NO)₂] was synthesized in moderate yield with high purity through a highly selective reaction route under mild reaction conditions. Its structure was elucidated by IR and UV/Vis spectroscopy, ESI-MS, and single-crystal X-ray diffraction studies. Furthermore, its ability to undergo controlled NO release was confirmed by ESI-MS, and a curve of the amount of NO released as a function of time within a simulated body fluid system was obtained by UV spectroscopy. The rate of NO release is controlled by changing the pH of the system. This is the first time that the decomposition of a POM has been used to produce therapeutic NO species. This study provides a new route to controlled-release technology for NO storage and targeted delivery. Copyright

Full text of DOI:10.1002/ejic.201201144

SHORT COMMUNICATION
DOI:10.1002/ejic.201201144
trans-Dinitrosyl-Substituted Hexamolybdate and Study of
Its Controllable NO Release
CLUSTER
ISSUE
Jiangwei Zhang,[a] Jian Hao,[a] Rao Naumaan Nasim Khan,[a]
Jin Zhang,*[a] and Yongge Wei*[a]
Keywords: Polyoxometalates / Structure elucidation / Nitrogen oxides / Drug delivery
On the basis of the well-developed N,NЈ-dicyclohexylcarbo-
diimide (DCC) imidoylization strategy, the novel trans-di-
trolled NO release was confirmed by ESI-MS, and a curve of
the amount of NO released as a function of time within a
simulated body fluid system was obtained by UV spec-
troscopy. The rate of NO release is controlled by changing
the pH of the system. This is the first time that the decompo-
sition of a POM has been used to produce therapeutic NO
species. This study provides a new route to controlled-re-
nitrosyl-substituted
polyoxometalate
(POM)
(NBu4)4-
[Mo6O17(ϵNO)2] was synthesized in moderate yield with
high purity through a highly selective reaction route under
mild reaction conditions. Its structure was elucidated by IR
and UV/Vis spectroscopy, ESI-MS, and single-crystal X-ray
diffraction studies. Furthermore, its ability to undergo con- lease technology for NO storage and targeted delivery.
in diverse disciplines, including catalysis, medicine, and ma-
Introduction
terials sciences.[12–14] Derivatives of POMs are usually pH
Nitric oxide (NO) is considered an extremely toxic gas,
sensitive; with a slight change in the pH of a system, POMs
but in the correct amount it has been identified as a crucial
have been shown to adjust their structures to form a more
biological signaling molecule in the cardiovascular, nervous,
stable state. This property is of great importance for the
and immune systems.[1,2] The discovery of its activity in the
precise, controlled delivery of gases. The structure of the
cardiovascular system was recognized with the Nobel Prize
Lindqvist hexamolybdate cluster has six reactive terminal
in Medicine and led to an explosion of research in NO bio-
oxygen atoms that may provide a high degree of NO stor-
logy and chemistry. Recently, materials such as polymers[3–5]
age. We expect that grafting of NO onto POMs through
and polymers functionalized with silica nanoparticles[6,7]
covalent bonding may provide a solution to the problem
and zeolites[8] have all been used for storage and delivery of
associated with the precise control of NO release. Since the
NO. Unfortunately, some of these NO donors suffer from
pioneer work of Knoth[15] and Pope,[16] the functionaliza-
drawbacks such as the generation of carcinogenic side prod-
tion of POMs through covalent grafting of organic ligands
ucts, low NO storage, and uncontrollable NO release, which
has been investigated extensively. As one important method
may limit their applicability.[9a,9b] Metal–organic frame-
for the functionalization of POMs, imidoylization has been
works (MOFs) have recently been used very successfully to
largely investigated by Maatta,[17] Proust,[18] Errington,[19]
deliver NO.[9c] Inspired by the similarities in the properties
and Peng and Wei.[20] Therefore, a series of organoimido
of polyoxometalates (POMs) and MOFs, our aim is to ex-
derivatives of the Lindqvist hexamolybdate cluster
tend NO storage and delivery materials by using function-
[Mo6O19]2– with remote active groups has been synthesized
alized POMs with a NO moiety.
previously.[21]
POMs are a unique class of inorganic nanoclusters con-
Inspired by the first synthesis of monosubstituted ni-
sisting of early transition metal ions such as vanadium and
trosyl POM derivatives reported by Proust,[22,23] we were
molybdenum in their highest oxidization states bridged by
interested in developing a synthesis of polynitrosyl-substi-
oxide anions. These clusters have fascinating photonic, elec-
tuted POM derivatives to further aid NO storage. Relative
tronic, and magnetic properties as well as unique chemical
to the large number of monosubstituted derivatives, exam-
reactivity and remarkable self-assembly properties.[10,11] The
unique properties of POMs has led to dramatic applications
ples of bifunctionalized derivatives are rare. The first exam-
ple of cis-disubstituted imido hexamolybdate was reported
by Maatta,[17,24] but this strategy to functionalize hexa-
[a] Department of Chemistry, Tsinghua University,
molybdate has some drawbacks: the material crystallizes
Beijing 100084, P. R. China
with unreacted hexamolybdate anions and monoderivatives,
which makes the separation of the desired bifunctionalized
products tedious and impractical. Moreover, the mecha-
nism for the formation of the disubstituted derivatives re-
E-mail: yonggewei@mail.tsinghua.edu.cn
jinjin_eva@163.com
Homepage: http://www.chem.tsinghua.edu.cn/publish/chemen/
2141/2011/20110405155030028624642/
20110405155030028624642_.html
Eur. J. Inorg. Chem. 2013, 1664–1671
1664
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjic.org
SHORT COMMUNICATION
mains unclear, and most examples reported are cis-disubsti- Table 1. Crystal data and structure refinement for 1.
tuted derivatives.[25]
Empirical formula
Size [mm3]
Formula weight
Crystal system
Space group
a [Å]
b [Å]
c [Å]
α [°]
β [°]
C64H144Mo6N6O19
0.550ϫ0.415ϫ0.355
1877.52
monoclinic
P21/c
24.028(3)
16.938(2)
16.632(4)
90.00
97.54(9)
90.00
6710(6)
Fortunately, on the basis of the DCC imidoylization
method developed by our group[26] as well as the DFT cal-
culations reported by our group[28] that show that cis-disub-
stituted derivatives are more stable than the corresponding
trans isomers, whereas the trans-disubstituted hexa-
molybdate is a kinetic, stable product, we believe that it
should be highly possible to graft NO directly onto POMs
through covalent bonding to give di/polysubstituted deriva-
tives. In this communication, a highly selective route to
form trans-dinitrosylated [Mo6O19]2– derivatives as the only
product is reported. We hope the results obtained here may
offer a new strategy for NO storage by using POMs as
frameworks.
γ [°]
V [Å3]
Z
4
Dcalcd. [gcm–3]
Temperature [K]
Tmax/Tmin
1.618
101(2)
0.6851/0.5698
1.153
Absorption coeff. [mm–1]
F(000)
3340
θ range [°]
Reflections collected
Rint
2.98 to 29.35
35565
0.0374
1.058
R1 = 0.0472, wR2 = 0.1009
R1 = 0.0672, wR2 = 0.1118
Results and Discussion
GOF on F2
Final R indices [IϾ2σ(I)]
R indices (all data)
Preparation of the Compound
Scheme 1 shows the synthesis of compound 1. The reac-
tion time, which can be monitored by UV/Vis spectroscopy,
was about 4 h. The hydrochloride salt is a proton carrier
that introduces the proton into the reaction mixture. The
likely role of the proton is to make a complex with DCC
and, hence, to increase the electrophilicity of DCC towards
attack of the oxo group of Mo–O. This reaction is highly
selective with easy manipulations, and the room-tempera-
ture reaction conditions are much milder than those used
in the imidoylization work by our group.[20] No obvious dif-
ferences in the results are obtained by increasing the reac-
tion temperature, and hence, the milder reaction conditions
were chosen.
typical structural features of dinitrosylated hexamolybd-
ates: the two terminal oxo atoms (Ot) of the hexamolybdate
cluster in the trans fashion are replaced by two NO groups,
and the NO+ ligands are bonded at an octahedral d4 metal
center. The short Mo–N bond lengths (1.703, 1.710 Å) and
the nearly linear Mo–N–O angles (178.5, 178.9°) are consis-
tent with a substantial degree of MoϵN triple bond charac-
ter.[29] The short N–O bond lengths (1.169, 1.180 Å) are
typical for a nitrosyl group. It was noted that the terminal
oxygen atoms, which belong to NO moieties, have large an-
isotropic displacement parameters compared to the other
oxygen atoms in the POMs. This has been observed in pre-
viously reported nitrosyl-substituted POMs[22,23] and could
result from significant disorder of these oxygen atoms,
probably as a result of the partial loss of the NO moieties
of the anions when 1 was exposed to the X-rays during data
collection, as we can see in the following section that 1 eas-
ily decomposes to release NO gas. The following structure
description will take type A with Mo–N bond lengths of
1.703 Å as an example. Notably, the bond lengths between
the Mo center bearing the nitrosyl group and the central
oxygen atom (Oc) are found to be 2.285 Å in 1, which is
slightly shorter than those of the corresponding Mo–Oc
(2.355 and 2.336 Å, respectively) because of the so-called
“trans influence”. This effect is in accordance with the fact
that the nitrosyl group, which is one of the strongest π-
acceptor ligands, is a stronger electron-withdrawing group
than the oxo group, and this indicates that the central Oc
atom shifts slightly toward the nitrosyl-bearing molybd-
Scheme 1. Synthesis of 1.
Crystallographic Structural Determinations
Summaries of the crystal data, data collection, and re-
finement parameters of compound 1 are given in Table 1.
Structural Description
Single-crystal X-ray diffraction studies confirmed that enum atoms. The nitrosyl-bearing molybdenum atoms are
two crystallographically different but chemically equivalent MoII and, therefore, should not attract the bridging oxygen
half cluster anions exist in the asymmetric unit, each of atoms as strongly as the oxo-MoVI center. As a result, the
which is located on a crystallographically symmetric center. bond lengths of 1.974 and 1.964 Å between the nitrosyl-
ORTEP drawings of the two anion moieties (types A and bearing Mo atoms and the bridging oxygen atom (Ob) are
B) in 1 are presented in Figure 1. Compound 1 displays the longer than the bonds lengths of 1.903 and 1.911 Å for the
Eur. J. Inorg. Chem. 2013, 1664–1671
1665
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjic.org
SHORT COMMUNICATION
Figure 1. ORTEP view and atomic labeling scheme for the cluster anion of 1 (type A and type B). Thermal ellipsoids are drawn at the
50% probability level.
other Mo atoms bearing terminal oxo groups and Ob. The brations of the C–H bond and the CH2 bending vibrations
Mo–N bond lengths are 1.703 Å in the cluster anion. Be- of the tetrabutylammonium cations, respectively.
cause the radius of nitrogen is larger than that of oxygen,
the Mo–N bond lengths should be longer than those of
Mo–Ot; however, the Mo–N and Mo–Ot (1.695 Å) bond
lengths are almost the same, and this may be because NO
possesses stronger electron-withdrawing properties than Ot.
This may also result from stronger feedback of the π elec-
trons from the t2g orbital of the Mo atom to the π2py* or-
bital of NO.[30,31] Hence, compared with the MoϵN bond
length of 1.72 Å for the monosubstituted derivatives of
hexamolybdate, the MoϵN bond length for 1 is slightly
shorter by about 0.02 Å.[20,32,33] Selected bond lengths and
angles are listed in Table 2.
Table 2. Selected bond lengths [Å] of the cluster anion for 1.
Mo1–N1
Mo1–O1
Mo3–O1
Mo1–O7A
Mo3–O7
1.703
2.285
2.336
1.964
1.911
O10–N1
Mo2–O1
Mo1–O3
Mo2–O3
Mo2–O9
1.169
2.355
1.974
1.903
1.695
Figure 2. IR spectrum of 1.
In comparison to the [Mo6O19]2– parent, for which the
UV absorption band is located around 325 nm,[32] the new
trans-disubstituted nitrosyl hexamolybdates show an ab-
Spectroscopic Characterization
The composition and structure of 1 was investigated by sorption band that is obviously bathochromically shifted to
elemental analysis and IR and UV/Vis spectroscopy. The 338 nm (Figure 3), and this corresponds to the lowest en-
IR spectrum (Figure 2) of 1 displays characteristic patterns ergy electronic transition from the HOMO, which is charac-
of the Lindqvist structure. Strong peaks assigned to the terized as the π-type nonbonding terminal oxygen and ni-
asymmetric stretching vibrations of Mo–Ot and Mo–Ob– trogen atoms, to the molybdenum d-type LUMO. The N
Mo (t = terminal, b = bridging) shift from 954 and atom of nitrosyl, which adopts sp hybridization, forms a
801 cm–1 in the hexamolybdate parent to 939 and 787 cm–1 MoϵN triple bond with the Mo atom as a result of the
in 1. The strong shoulder peak around 962 cm–1 is diagnos- replacement of one of the terminal oxygen atoms of the
tic for the disubstituted nitrogenous derivatives of a hexa- hexamolybdate. There is one d sp σ-bonding interaction
molybdate with Mo–N multiple bonds, as previously re- and two π-type (d–π) bonding interactions. The second
ported,[24] and this peak is obviously shifted to lower wave- band near 254 nm in [Mo6O19]2–, which originates from the
numbers relative to that of the corresponding mononitrosyl d–π transition from the oxygen π-type nonbonding orbitals
derivative. The bands at 1568 and 1662 cm–1 are associated to the molybdenum d-type LUMO, has no obvious varia-
with the stretching vibrations of the N–O bond of the ni- tion in the case of 1, which indicates that the incorporated
trosyl group. In addition, the peaks around 2900 cm–1 and nitrosyl ligands have little effect on the skeleton of the hexa-
the band at 1383 cm–1 are assigned to the stretching vi- molybdate and that the energy levels of the oxygen π-type
Eur. J. Inorg. Chem. 2013, 1664–1671
1666
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjic.org
SHORT COMMUNICATION
nonbonding orbitals in these related cluster anions are al- KH2PO4. The whole decomposition process of 1 was inves-
most identical.
tigated and confirmed by ESI-MS (Figure 4) in the follow-
ing way: The trans-disubstituted nitrosyl compound
(NBu4)4[Mo6O17(ϵNO)2] was initially attacked by H2O to
release NO and to afford the monosubstituted derivative.
Then, the monosubstituted derivative (NBu4)3[Mo6O18-
(ϵNO)] can undergo attack by another molecule of H2O
with complete release of NO to give the final product
(NBu4)2[Mo6O19], which could be used to synthesize
(NBu4)4[Mo6O17(ϵNO)2] (1) by the hexamolybdate reac-
tion strategy that was developed by our group.[26]
Compound 1 was subjected to ESI-MS testing, and three
major peeks were found: m/z = 226.52 [Mo6O17(NO)2]4–,
575.65 (Bu4N)[H+][Mo6O17(NO)2]2–, 1393.68 (Bu4N)2-
[H+][Mo6O17 (NO)2]– (Figure 4, a). The two-step decompo-
sition process of 1 was confirmed through ESI-MS versus
time analysis. Compound 1 was first placed in the simulated
body fluid for 6 h and then filtered out and dissolved in
acetonitrile for ESI-MS analysis (Figure 4, b). The peak at
m/z = 226.52 belongs to [Mo6O17(ϵNO)2]4–, and the other
major peaks belong to the monosubstituted compound
(NBu4)3[Mo6O18(ϵNO)] were assigned as follows: m/z =
296.95 [Mo6O18(ϵNO)]3–, 447.24 [H+][Mo6O18(ϵNO)]2–,
1137.72 (Bu4N)[H+][Mo6O18(ϵNO)]–, 1379.91 (Bu4N)2-
[Mo6O18(ϵNO)]–. It is clear that most of 1 in this buffer
solution was converted into monosubstituted (NBu4)3-
[Mo6O18(ϵNO)]. Another sample of 1 was treated in the
same way but was filtered and dissolved in acetonitrile after
24 h. The result was quite different from that above. It is
Figure 3. UV spectra of (NBu4)4[Mo6O17(ϵNO)2], (NBu4)3-
[Mo6O18(ϵNO)], and (NBu4)2[Mo6O19] in CH3CN.
The structure of the trans-disubstituted nitrosyl hexa-
molybdate obtained in this work was further elucidated by
ESI-MS. The major isotopic cluster located at m/z = 226.5
was assigned to [Mo6O17(NO)2]4– (calcd. m/z = 226.9).
NO Release Study
NO is an extremely important biological signaling mole- clear that the peaks belonging to the monosubstituted com-
cule, and its delivery from a storage material is attractive pound (NBu4)3[Mo6O18(ϵNO)] at m/z = 1379.94 (Bu4N)2-
for many in vitro and in vivo antibacterial, antithrombotic, [Mo6O18(ϵNO)]– and 567.87 (Bu4N)[Mo6O18(ϵNO)]2– re-
and wound-healing applications.[1,2,34–36] However, to the mained; however, these peaks have low intensity, which in-
best of our knowledge, the use of POMs as a carrier for NO dicates that most of monosubstituted compound had de-
storage and delivery has never been reported. Fortunately, composed into hexamolybdate (NBu4)2[Mo6O19]. In Fig-
according to our previous ESI-MS study[37] on organo- ure 4 (c), the three higher peaks belong to hexamolybdate:
imido derivatives of POMs, these compounds are unstable m/z = 1121.88 (Bu4N)[Mo6O19]–, 880.56 [H+][Mo6O19]–,
in nearly neutral or basic aqueous solutions. It was con- 440.39 [Mo6O19]2–. Thus, the whole recycling process is il-
firmed that the MoϵN triple bonds are frail and that they lustrated in Figure 5.
can be attacked by H2O or OH–, which leads to the decom-
The release of NO was confirmed by the following
position of the title molecules. They decompose into method. Compound 1 (2 g) and the buffer solutions were
[Mo6O19]2– or [Mo8O26]4–, depending on the pH value of introduced into a 25 mL round-bottomed flask that was se-
the solution and the ligand fragments correspondingly re- aled with a rubber plug and connected to another 5 mL
leased. Thus, we came to realize that this property could be round-bottomed flask, which was turned upside down and
applied to develop a novel controlled-release technology for immersed in water to seal it. The colorless gas released from
NO drug delivery. Under normal circumstances, NO inter- the first flask replaced the water in the second flask. When
acts strongly enough with POMs through covalent bonds, the second flask was full of gas, it was removed from the
but with a change in the pH of the solution, the MoϵN water and fitted with a rubber plug. Subsequently, it was
triple bonds can be broken to release NO from the POMs exposed to oxygen, and the color of the gas inside the flask
at a required time. The entire reservoir of stored NO can changed from transparent to reddish-brown immediately.
be released by a triggering mechanism under suitable condi- This observation confirmed that the gas released from com-
tions. The preferred trigger for NO release is exposure to pound 1, and hence initially present in the flask, was NO,
water or body fluids at room or body temperature under a because its oxidation by exposure to oxygen caused a
suitable pH range. Coincidentally, the pH values of body change in color as a result of the production of reddish-
fluids range from 7.3 to 7.4, and these slightly basic condi- brown NO2 (Figure 6).
tions are perfect for the decomposition of the title mole-
As we know, the amount of NO released from the de-
cules to release NO. We placed 1 in a simulated body fluid, composition of (NBu4)4[Mo6O17(ϵNO)2] (1 mmol) is just
which was made up of a buffer solution of Na2HPO4 and 60 mg. To detect precisely the amount of NO released, UV
Eur. J. Inorg. Chem. 2013, 1664–1671
1667
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjic.org
SHORT COMMUNICATION
Figure 4. Compound 1 (a) and the two-step decomposition process (b and c) investigated by ESI-MS.
spectrophotometry was used. Initially, we attempted to absorbance of (NBu4)4[Mo6O17(ϵNO)2], (NBu4)3[Mo6O18-
monitor NO release on the basis of a decrease in the d–d (ϵNO)], and (NBu4)2[Mo6O19] versus concentration were
transition, which is related to the MoϵNO units in the UV obtained at 338, 331, and 325 nm respectively (Figure 7, see
spectrum; however, this was too weak to be detected. As a also the Exp. Sect. for details).
compromise, the charge-transfer band was alternatively
From the data we obtained from the NO release test, we
used to monitor the release of NO, which may cause devia- can calculate the amount of NO released from the system,
tion to some extent. The standard working curves of the and then these data can be converted into the amount of
Eur. J. Inorg. Chem. 2013, 1664–1671
1668
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjic.org
SHORT COMMUNICATION
Figure 5. The decomposition process of (NBu4)4[Mo6O17(ϵNO)2]
and NO storage and releasing cycle.
Figure 8. The amount of NO released at different pH values versus
time.
Conclusions
In summary, through a highly selective reaction route the
trans-dinitrosyl hexamolybdate [Mo6O17(NO)2]4– was syn-
Figure 6. Crystal of compound 1 (left), and crystals of the final thesized in reasonable yield. Its structure was elucidated by
decomposition substance (right), and characterization of free NO
released (middle).
IR and UV/Vis spectroscopy, ESI-MS, and single-crystal X-
ray diffraction techniques. Furthermore, compound 1 was
unstable and could easily be attacked by H2O or OH– in
neutral or basic solutions, which resulted in the release of
the corresponding NO ligand fragments. This was con-
firmed by ESI-MS, and a precise curve of the amount of
NO released versus time was obtained through UV spectro-
photometric studies. Taking advantage of this releasing
property is a significant step towards the development of
new NO materials for controllable storage and delivery.
This is the first time that a POM has been used for the
controlled production of the therapeutic NO moiety. With
further encapsulation into suitable MOFs, POMs may be
an ideal candidate to ultimately produce NO in vivo from
biologically available sources without resulting in toxicity
issues. Future studies are aimed at the design of compounds
for the site-specific generation of NO. This may open up a
new route to develop novel, controlled-release technology
for NO storage and delivery. Related studies may provide
new possibilities in the development of pharmaceutical
products. Related work is under way in our laboratory.
Figure 7. The standard working curve of (NBu4)4[Mo6O17-
(ϵNO)2], (NBu4)3[Mo6O18(ϵNO)], and (NBu4)2[Mo6O19].
Experimental Section
General Methods and Materials: All syntheses and manipulations
were performed in open air. (NBu4)4[Mo8O26] was synthesized ac-
NO released at different pH values as a function of time
cording to the improved literature method[20] and dried before use.
(Figure 8). It is obvious that the rate of NO release in-
Hydroxylamine hydrochloride was also dried before use. Aceto-
creases as the pH value of the solution is increased. The
nitrile was dried by heating at reflux in the presence of CaH2 and
time required for complete decomposition of 1 at pH 7.2 is
was distilled prior to use. N,NЈ-Dicyclohexylcarbodiimide (DCC)
nearly 30 h, which is 4 h longer than that at pH 8.1. This
was used directly without further purification. IR spectra were
means that the rate of NO release can be controlled simply
by changing the pH value of the simulated body fluid sys-
tem.
measured by using KBr pellets and recorded with a Perkin–Elmer
FTIR spectrometer. UV/Vis spectra were measured in acetonitrile
with a UV2100s spectrophotometer. Mass spectra were obtained by
Eur. J. Inorg. Chem. 2013, 1664–1671
1669
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjic.org
SHORT COMMUNICATION
using an ion trap mass spectrometer (Thermofisher LTQ). Negative
mode was chosen for the experiments (capillary voltage 33 V). Sam-
ple solution (in acetonitrile) was infused into the ESI source at a
flow rate of 300 μLmin–1.
respectively. By using the linear equation, the precise amount of
each substance could be calculated at different times.
Acknowledgments
Synthesis of (NBu4)4[Mo6O17(NO)2] (1): A mixture of (NBu4)4-
[Mo8O26] (2.16 g, 1 mmol), hydroxylamine hydrochloride (0.184 g,
2.67 mmol), tetrabutylammonium bromide (0.428 g, 1.33 mmol),
and DCC (0.687 g, 3.33 mmol) was dissolved in anhydrous acetoni-
trile (50 mL) and then allows to react at room temperature for
about 4 h. Then, the reaction solution was filtered to remove the
white 1,3-dicyclohexylurea (DCU) precipitate, and a dark-brown
solution was obtained; then, the filtrate was poured into ether,
which resulted in precipitation. After the solution cleared, the su-
pernatant liquid was poured off. The solid depositing in the bottom
of the beaker was redissolved in acetone and filtered to remove a
large amount of unreacted octamolybdate. The acetone was al-
lowed to slowly evaporate, the product deposited from the filtrate
as a black cubic solid. After recrystallization (acetone and aceto-
nitrile = 1:2, 10 mL), the title compound could be obtained as a
black crystalline products (60% yield based on Mo).
C64H144N6Mo6O19 (1877.52): calcd. H 7.73, C 40.94, N 4.48, O
16.19, Mo 30.66; found H 7.78, C 40.95, N 4.46, O 16.21, Mo
This work was financially supported by the National Natural Sci-
ence Foundation of China (NSFC) (grant number 91022010).
[1] R. M. J. Palmer, A. G. Ferrige, S. Moncada, Nature 1987, 327,
524.
[2] M. A. Marletta, Trends Biochem. Sci. 1989, 14, 488–492.
[3] P. G. Parzuchowski, M. C. Frost, M. E. Meyerhoff, J. Am.
Chem. Soc. 2002, 124, 12182–12191.
[4] B. Wu, B. Gerlitz, B. W. Grinnell, M. E. Meyerhoff, Biomateri-
als 2007, 28, 4047–4055.
[5] F. De Rosa, M. R. Kibbe, S. F. Najjar, M. L. Citro, L. K.
Keefer, J. A. Hrabie, J. Am. Chem. Soc. 2007, 129, 3786–3787.
[6] H. P. Zhang, G. M. Annich, J. Miskulin, K. Stankiewicz, K.
Osterholzer, S. I. Merz, R. H. Bartlett, M. E. Meyerhoff, J.
Am. Chem. Soc. 2003, 125, 5015–5024.
[7] J. H. Shin, M. H. Schoenfisch, Chem. Mater. 2008, 20, 239–
249.
[8] P. S. Wheatley, A. R. Butler, M. S. Crane, S. Fox, B. Xiao, A. G.
Rossi, I. L. Megson, R. E. Morris, J. Am. Chem. Soc. 2006,
128, 502–509.
30.65. UV/Vis (MeCN): λmax = 338 nm. IR (KBr pellet): ν = 2961,
˜
2874, 1663, 1568 1383, 962, 939, 885, 787 cm–1. MS (MeCN, ESI):
m/z
=
226.52 [Mo6O17(NO)2]4– (calcd. 226.91), 575.65
[9] a) K. D. Kroncke, C. V. Suschek, J. InVest. Dermatol. 2008,
128, 258–260; b) M. Mowbray, X. J. Tan, P. S. Wheatley, R. E.
Morris, R. B. Weller, J. Invest. Dermatol. 2008, 128, 352–360;
c) N. J. Hinks, A. C. McKinlay, B. Xiao, P. S. Wheatley, R. E.
Morris, Microporous Mesoporous Mater. 2009, 129, 330–334.
[10] I. V. Kozhevnikov, Chem. Rev. 1998, 98, 171–198.
[11] J. T. Rhule, C. L. Hill, D. A. Judd, Chem. Rev. 1998, 98, 327–
357.
[12] Y. P. Jeannin, Chem. Rev. 1998, 98, 51–76.
[13] E. Coronado, P. Day, Chem. Rev. 2004, 104, 5419–5422.
[14] M. Sadakane, E. Steckhan, Chem. Rev. 1998, 98, 219–237.
[15] W. H. Knoth, J. Am. Chem. Soc. 1979, 101, 759–760.
[16] F. Zonnevijlle, M. T. Pope, J. Am. Chem. Soc. 1979, 101, 2731–
2732.
(Bu4N)[H+][Mo6O17(NO)2]2– (calcd. 575.55), 1393.68 (Bu4N)2-
[H+][Mo6O17(NO)2]– (calcd. 1393.58).
X-ray Crystallographic Structural Determinations:
single crystal having approximate dimensions
A
suitable
of
0.550ϫ0.415ϫ0.355 mm3 was selected. Data collection was per-
formed at 100 K by using graphite-monochromated Mo-Kα radia-
tion (λ = 0.71073 Å). Data reduction, cell refinement, and experi-
mental absorption correction were performed with the software
package of Rigaku RAPID AUTO (Rigaku, 1998, version 2.30).
Structures were solved by direct methods and refined against F2
by full-matrix least-squares. All non-hydrogen atoms were refined
anisotropically. Hydrogen atoms were generated geometrically. All
calculations were carried out by the program package of
SHELXTL version 5.1.[27]
[17] J. B. Strong, G. P. A. Yap, R. Ostrander, L. M. Liable-Sands,
A. L. Rheingold, R. Thouvenot, P. Gouzerh, E. A. Maatta, J.
Am. Chem. Soc. 2000, 122, 639–649.
[18] A. Proust, R. Thouvenot, M. Chaussade, F. Robert, P. Gouz-
erh, Inorg. Chim. Acta 1994, 224, 81–95.
CCDC-923001 contains the supplementary crystallographic data
for this compound. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.cam.
ac.uk/data_request/cif.
[19] W. Clegg, R. J. Errington, K. A. Fraser, S. A. Holmes, A.
Schäfer, J. Chem. Soc., Chem. Commun. 1995, 455–456.
[20] Y. G. Wei, B. Xu, C. L. Barnes, Z. H. Peng, J. Am. Chem. Soc.
2001, 123, 4083–4084.
NO Releasing Test: The mononitrosyl-substituted compound of
(NBu4)3[Mo6O18(ϵNO)] was first synthesized according to the pro-
tocol presented by Proust[22] before the UV spectroscopy test. Ac-
cording to Lambert–Beer’s law, the absorbance of a solution has
a simple linear relationship with its concentration. Thus, through
making the standard working curve of the absorbance of
(NBu4)4[Mo6O17(ϵNO)2], (NBu4)3[Mo6O18(ϵNO)], and (NBu4)2-
[Mo6O19] versus different concentrations, the linear equation of the
absorbance of these compounds with their concentrations can be
simply obtained (Figure 7).
[21] J. Zhang, F. P. Xiao, J. Hao, Y. G. Wei, Dalton Trans. 2012, 41,
3599–3615.
[22] P. Gouzerh, Y. Jeannin, A. Proust, F. Robert, Angew. Chem.
1989, 101, 1377; Angew. Chem. Int. Ed. Engl. 1989, 28, 1363–
1364.
[23] A. Proust, F. Robert, P. Gouzerh, Q. Chen, J. Zubieta, J. Am.
Chem. Soc. 1997, 119, 3523–3535.
[24] J. B. Strong, R. Ostrander, A. L. Rheingold, E. A. Maatta, J.
Am. Chem. Soc. 1994, 116, 3601–3602.
[25] X. D. Liu, Y. Q. Qiu, S. L. Sun, C. G. Liu, Z. M. Su, J. Theor.
Comput. Chem. 2010, 9, 219–223.
[26] L. Xu, M. Lu, B. B. Xu, Y. G. Wei, Z. H. Peng, D. R. Powell,
Angew. Chem. 2002, 114, 4303; Angew. Chem. Int. Ed. 2002,
41, 4129–4132.
[27] G. M. Sheldrick, Acta Crystallogr., Sect. A 2008, 64, 112–122.
[28] C. L. Lv, J. J. Hu, H. Zhou, Z. Li, R. N. N. Khan, Y. G. Wei,
Chem. Eur. J. 2012, 18, 8681–8691.
[29] L. S. Wang, L. Zhu, P. C. Yin, W. W. Fu, J. K. Chen, J. Hao,
F. P. Xiao, C. L. Lv, J. Zhang, L. Shi, Q. Li, Y. G. Wei, Inorg.
Chem. 2009, 48, 9222–9235.
Preparation of Buffer Solutions: The concentrations of both the
Na2HPO4 and KH2PO4 solutions were 1/15 m. For the preparation
of pH 7.1 buffer solutions, 72 mL of Na2HPO4 and 28 mL of
KH2PO4 were mixed together, whereas for the preparation of
pH 8.2 buffer solutions, 95.8 mL of Na2HPO4 and 4.2 mL of
KH2PO4 were mixed together. The compound was removed from
the simulated body fluid by extraction and dissolved in acetonitrile
and then tested for the characteristic absorbance of (NBu4)4-
[Mo6O17(ϵNO)2], (NBu4)3[Mo6O18(ϵNO)], and (NBu4)2[Mo6O19],
Eur. J. Inorg. Chem. 2013, 1664–1671
1670
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjic.org
SHORT COMMUNICATION
[30]
[31]
[34] C. F. Pradeep, D. Long, G. N. Newton, Y. Song, L. Cronin,
Angew. Chem. 2008, 120, 4460; Angew. Chem. Int. Ed. 2008,
47, 4388–4391.
[35] H. F. Zhu, B. Ka, F. Murad, World J. Surg. 2007, 31, 624–631.
[36] M. R. Miller, I. L. Megson, Br. J. Pharmacol. 2007, 151, 305–
321.
S. C. Liu, H. Z. Zhu, J. Zubieta, Polyhedron 1989, 8, 2473–
2480.
A. Proust, P. Gouzerh, F. Robert, Inorg. Chem. 1993, 32, 5291–
5298.
[32] Y. Du, A. L. Rheingold, E. A. Maatta, J. Am. Chem. Soc. 1992,
114, 345–346.
[37] Q. Li, P. C. Yin, L. Shi, Y. G. Wei, Eur. J. Inorg. Chem. 2009,
[33] R. A. Roesner, S. C. McGrath, J. T. Brockman, J. D. Moll,
D. X. West, J. K. Swearingen, A. Castineiras, Inorg. Chim. Acta
2003, 342, 37–47.
5227–5232.
Received: September 25, 2012
Published Online: February 8, 2013
Eur. J. Inorg. Chem. 2013, 1664–1671
1671
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim