Tricarbonylmanganese(I) and -rhenium(I) complexes of imidazol-based phosphane ligands: Influence of the substitution pattern on the CO release properties

Article abstract of DOI:10.1002/ejic.200900650

Tricarbonylmanganese(I) and -rhenium(I) complexes of the imidazolylphosphane ligands tris(imidazol-2-yl)phosphane (2-TIP^H), tris(N-methylimidazol-2-yl)phosphane (2-TIP^NMe), and tris[2-isopropylimidazol-4(5)-yl]phosphane (4-TIP/^P

Full text of DOI:10.1002/ejic.200900650

FULL PAPER
DOI: 10.1002/ejic.200900650
Tricarbonylmanganese(I) and –rhenium(I) Complexes of Imidazol-Based
Phosphane Ligands: Influence of the Substitution Pattern on the CO Release
Properties
Peter C. Kunz,*[a] Wilhelm Huber,[a] Alfonso Rojas,[b] Ulrich Schatzschneider,[b] and
Bernhard Spingler[c]
Keywords: Manganese / Rhenium / CO-releasing molecules / N ligands / Tripodal ligands
Tricarbonylmanganese(I) and -rhenium(I) complexes of the
imidazolylphosphane ligands tris(imidazol-2-yl)phosphane
(2-TIPH), tris(N-methylimidazol-2-yl)phosphane (2-TIPNMe),
and tris[2-isopropylimidazol-4(5)-yl]phosphane (4-TIPiPr) as
well as the phosphane oxide (4-TIPOiPr) and sulfide (4-
TIPSiPr) ligands were prepared. These tris(imidazolyl) ligands
act as N,N,N-tripodal chelating ligands. The solid-state
structures of the manganesecomplexes [(2-TIPNMe)Mn(CO)3]-
OTf and [(4-TIPSiPr)Mn(CO)3]OTf as well as the rhenium
compound [(4-TIPOiPr)Re(CO)3]OTf were determined by X-
ray diffraction. The potential of these complexes as photoac-
tivatable CO-releasing molecules (CORMs) was studied with
the UV/Vis spectroscopy-based myoglobin assay. Within the
series of compounds prepared, the substitution pattern of the
imidazolyl groups was found to significantly influence the
CO-release efficiency and stoichiometry.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
bon monoxide. An increasing number of such “CO-releas-
ing molecules” (CORMs) are being studied to optimize
their CO-release characteristics and achieve sufficient water
solubility for therapeutic applications.[7–9] Whereas Motter-
lini et al. have pioneered the use of carbonylruthenium com-
pounds, with tricarbonylchloro(glycinato)ruthenium(II)
(CORM-3) as the CO-releasing molecule most commonly
employed in biological studies at present,[10] more recently
carbonyl(pyrone)iron and -molybdenum complexes
(CORM-F7 and CORM-F10) have also received consider-
able attention.[11–13] Whereas in these complexes the CO re-
lease is usually triggered by ligand-substitution reactions in
aqueous solution, an alternative approach has explored the
light-induced liberation of carbon monoxide from dark-
stable carbonylmanganese complexes, like [Mn2(CO)10]
(CORM-2).[14] In particular, the tricarbonyl complex
[(tpm)Mn (CO)3]PF6 was shown to release CO upon UV
radiation and exhibit cytotoxic activity against cancer cells
while being inactive even after prolonged exposure in the
dark.[15,16] Although the number of studies on carbon-
ylmetal CORMs has significantly grown over recent years,
very few systematic studies of the factors determining the
mechanism of CO release have been carried out.[17,18]
Introduction
For a long time, carbon monoxide (CO) was mostly seen
as a dangerous air pollutant because of its properties as an
odorless and colorless gas that is highly toxic to humans
due to its interference with the oxygen transport in blood.
In recent years, it has, however, become clear that carbon
monoxide is endogenously produced in the human body by
tightly controlled enzymatic degradation of heme and
serves as an important small-molecule messenger, much like
nitric oxide (NO).[1–3] In addition, deliberate application of
CO was found to give rise to a number of beneficial physio-
logical effects because of its antiinflammatory, antioxidat-
ive, and antiapoptotic activities. In animal experiments, it
was also shown to affect ocular hypertension as well as co-
agulation processes associated with transplantations.[4–6]
As CO itself is difficult to dose and is a highly toxic gas,
there is currently significant interest in the application of
carbonylmetal complexes as a solid “storage form” for car-
[a] Institut für Anorganische Chemie und Strukturchemie I, Hein-
rich-Heine-Universität Düsseldorf,
Universitätsstr. 1, 40225 Düsseldorf, Germany
Fax: +49-211-81-12287
E-mail: peter.kunz@uni-duesseldorf.de
Here, we report on the synthesis and characterization of
a series of Mn(CO)3 and Re(CO)3 complexes of different
imidazol-2-yl and imidazol-4(5)-ylphosphane ligands. Since
the introduction of the tris(pyrazolyl)boranes (tp) by Trofi-
menko, scorpionate ligands containing N-donor atoms have
been intensively studied and are well known as ligands for
complexes used in biomedical applications.[19–21] The tris-
[b] Lehrstuhl für Anorganische Chemie
I - Bioanorganische
Chemie, Ruhr-Universität Bochum NC 3/74,
Universitätsstr. 150, 44801 Bochum, Germany
Fax: +49-234-32-14378
E-mail: ulrich.schatzschneider@rub.de
[c] Anorganisch-Chemisches Institut, Universität Zürich-Irchel,
Winterthurerstr. 190, 8057 Zürich, Switzerland
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejic.200900650.
5358
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2009, 5358–5366

MnI- and ReI(CO)3 Complexes of Imidazol-Based Phosphane Ligands
(imidazol-2-yl)phosphanes and tris[imidazol-4(5)-yl]phos- were able to structurally characterize complex 6 (Figure 1),
phanes used in this study are neutral analogues of the tp where two diphenyl[imidazol-4(5)-yl]phosphane ligands (4-
ligand in which the hydrolytically unstable B–N bonds have MIPiPr) are coordinated to the Re(CO)3 core. When the
been replaced by more stable P–C bonds.[22,23] To assess the phosphorus atom of the 4-TIPiPr is oxidized or modified
bioavailability of these new complexes, their stability and by sulfurization, however, only the tripodal N,N,N-binding
distribution coefficient in physiological media have been mode is possible. Espinet et al. reported on the formation
studied, followed by an investigation of light-induced CO of analogous Mo(CO)3 complexes of tris(pyridin-2-yl)phos-
release from the Mn complexes.
phane (Ppy3)-based ligands. They found that in the reaction
of [Mo(CO)6] or [Mo(CO)4(nbd)] (nbd:norbornadiene)
with Ppy3, intermediates form in which the Ppy3 ligand is
P,N,N-bound, whereas the final product shows N,N,N-coor-
Results and Discussion
The imidazol-2-ylphosphanes 2-TIPH and 2-TIPNMe dination.[28]
were prepared according to the procedures reported by Wu
et al.[24] and Brown et al.[25] The ligands 4-TIPiPr, 4-TIPOiPr
Complex 5a could not be prepared in analytically pure
form as it was always found to be contaminated by small
,
and 4-MIPiPr were synthesized as reported pre- amounts of 4a. Additionally, the presence of hydrogen sul-
viously.[22,23,26] For the synthesis of 4-TIPSiPr, the sulfuriz- fide could be recognized by its characteristic smell. Obvi-
ation reaction was carried out in ethanol under reflux by ously, traces of water lead to hydrolysis of the 4-TIPSiPr
using 4-TIPiPr and elemental sulfur.
ligand during the reaction.
The rhenium complexes 1a–5a (Figure 1) were prepared
The synthesis of manganese complexes 1b–5b (Figure 1)
by addition of a solution of the corresponding ligand to a was straightforward. After in situ preparation of [Mn(CO)3-
solution of [Re(H2O)3(CO)3]Br in methanol.[27] In this reac- (solv)3]OTf by abstraction of the bromide ion from
tion, the phosphane ligand 4-TIPiPr was found to coordi- [Mn(CO)5Br] with silver triflate, the respective ligand was
nate exclusively in the C3v-symmetric N,N,N-binding mode, added in acetone to obtain the desired complexes in good
and compound 3a was obtained in excellent yield. On the yield.
other hand, when 4-TIPiPr was treated with [Re(CO)5Br]
The IR stretching frequencies and chemical shifts of the
under the same conditions, a mixture of products was ob- 31P NMR resonances of all complexes are reported in
tained, as can be seen in the 31P{1H} NMR spectrum of Table 1. All complexes 1–5 show two bands in the carbonyl
the reaction mixture. Very likely, the 4-TIPiPr ligand adopts region typical for C3v-symmetrical compounds. In addition,
1
different coordination modes here, which might also involve their H NMR spectra show only one set of signals for the
binding of the phosphorus atom to the metal center. As an protons of the three equivalent imidazolyl rings. Although
example of such a P-bound imidazol-4(5)-ylphosphane, we the phosphorus atom is not coordinated to the metal center,
Table 1. IR and 31P{1H} NMR spectroscopic data of complexes [LM(CO)3]+ (1–5) and [L2Re(CO)3Br] (6).
L
M
Complex
ν(CO) [cm–1]
31P{1H} δ [ppm]
2-TIPH
Re
Mn
Re
Mn
Re
Mn
Re
Mn
Re
Mn
Re
1a
1b
2a
2b
3a
3b
4a
4b
5a
5b
6
1922, 2031
1915, 2042
1886, 2007
1919, 2033
1902, 2021
1933, 2027
1914, 2026
1935, 2031
1908, 2029
1929, 2032
1920, 1948, 2031
–99.2
–101.7
–113.5
–115.7
–101.4
–103.6
+3.0
+1.3
–3.4
–7.0
–16.1
2-TIPNMe
4-TIPiPr
4-TIPOiPr
4-TIPSiPr
4-MIPiPr
Figure 1. Manganese and rhenium complexes 1–6 investigated in this study.
Eur. J. Inorg. Chem. 2009, 5358–5366
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5359

P. C. Kunz, W. Huber, A. Rojas, U. Schatzschneider, B. Spingler
FULL PAPER
the 31P{1H} NMR signal of the PIII atoms in 1–3 shifts to
higher field by about 25 ppm upon coordination of the li-
gand to the M(CO)3 moiety. A similar observation was
made by Johnson for ligands of the type P(CH2-
NHR)3.[29–32] The shift of the 31P{1H} NMR signal of 6,
which is a classical coordination shift, is 15 ppm to a lower
field. The 1H NMR spectrum of bis(ligand) complex 6
shows one set of signals for the two coordinated ligands,
and in the IR spectrum three bands typical of a Cs-symmet-
rical complex are found.[33]
Figure 2. Solid-state structure of 2b. The counterion and H atoms
are omitted for clarity. Displacement ellipsoids are drawn at the
50% level.
Solid-State Structures
Several of the new complexes could be characterized by
X-ray structure analysis of suitable single crystals. Complex
2b crystallizes in the monoclinic space group P21/c. Crystals
Compound 5b crystallizes with a molecule of diethyl
were obtained by slow diffusion of diethyl ether into a solu- ether in the lattice as 5b·C4H10O in the orthorhombic space
tion of 2b in methanol. Alternatively, from a solution of 2b group Pnma (see Figure 4). Cation, anion, and solvate
in acetone, the solvate 2b·(CH3)2CO was crystallized. In this molecules are all dissected by the mirror plane of the space
case, the space group was determined as triclinic P1. The group. As found in the ReI complex 4a, the MnI center is
¯
metrical parameters of the complex cation are identical in also in a octahedral coordination environment, bound to
both structures, thus only the former structure is shown in three CO ligands and three nitrogen donor atoms from the
Figure 2. The parameters are comparable to those of tris(pyr- facially coordinating 4-TIPSiPr ligand. As for 2b, the metri-
azolyl)methane (tpm) complexes [Mn(CO)3(tpm)]+.[15,34–38]
cal parameters of 5b are comparable to those of tris(pyrazo-
Compound 4a crystallizes with two solvent molecules in lyl)methane (tpm) complexes [Mn(CO)3(tpm)]+.[15,34–38] Se-
the lattice as 4a·H2O·(CH3)2CO in the triclinic space group lected bond lengths and angles of the N,N,N-bound
iPr
¯
P1 (see Figure 3). The 4-TIPO ligand is coordinated to [LM(CO)3]X compounds 2b, 2b·(CH3)2CO, 4a·H2O·(CH3)2-
the rhenium atom in a tripodal N,N,N-fashion. In addition, CO, and 5b·(C2H5)2O are summarized in Table 2.
the ReI center is facially bound to three CO ligands. The
The bis(ligand) complex 6 crystallizes in the monoclinic
metrical parameters are comparable to those of tris(pyr- space group P21/c. The two imidazolylphosphane ligands
azolyl)methane (tpm) complexes of Re(CO)3.[39–42]
are bound to the fac-Re(CO)3 core through their phospho-
Table 2. Selected bond lengths [Å] and angles [°] for the N,N,N-bound [LM(CO)3]X compounds 2b, 2b·(CH3)2CO, 4a·H2O·(CH3)2CO,
and 5b·(C2H5)2O.
d [Å]
2b
2b·(CH3)2CO
4a·H2O·(CH3)2CO
5b·(C2H5)2O
M–C(1)
M–C(2)
M–C(3)
M–N(1)
M–N(2)
M–N(3)
C(1)–O(1)
C(2)–O(2)
C(3)–O(3)
1.792(3)
1.821(3)
1.813(3)
2.053(2)
2.062(2)
2.069(2)
1.149(3)
1.137(3)
1.142(3)
1.794(3)
1.802(3)
1.811(3)
2.058(2)
2.0516(18)
2.055(2)
1.153(3)
1.151(3)
1.140(3)
1.914(8)
1.953(8)
1.943(8)
2.226(6)
2.211(5)
2.229(5)
1.152(10)
1.113(10)
1.132(10)
1.808(3)
1.804(4)
–
2.105(2)
2.123(3)
–
1.144(4)
1.140(5)
–
Angle [°]
C(1)–M–C(2)
C(1)–M–C(3)
C(2)–M–C(3)
N(1)–M–N(2)
N(1)–M–N(3)
N(2)–M–N(3)
C(1)–M–N(1)
C(1)–M–N(2)
C(1)–M–N(3)
C(2)–M–N(1)
C(2)–M–N(2)
C(2)–M–N(3)
C(3)–M–N(1)
C(3)–M–N(2)
C(3)–M–N(3)
89.33(12)
89.86(13)
90.87(13)
86.50(9)
86.88(9)
85.93(9)
178.11(11)
93.01(11)
91.27(11)
91.08(11)
176.40(19)
91.28(11)
91.98(11)
91.88(11)
177.58(11)
89.63(12)
91.58(13)
89.92(12)
87.05(7)
86.71(7)
85.24(8)
177.31(11)
90.90(10)
92.90(11)
92.37(10)
178.40(10)
91.76(11)
90.23(10)
91.57(10)
175.23(11)
91.9(3)
90.0(3)
92.3(3)
84.9(2)
86.0(2)
85.1(2)
175.9(3)
91.5(3)
91.7(3)
91.6(3)
174.6(2)
90.6(3)
92.1(3)
92.0(3)
176.6(3)
89.19(12)
92.05(12)
–
88.39(8)
86.71(11)
–
176.99(10)
90.17(10)
90.60(10)
92.28(10)
179.08(14)
–
–
–
–
5360
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MnI- and ReI(CO)3 Complexes of Imidazol-Based Phosphane Ligands
rus atoms, and the sixth position in the distorted octahedral
environment is occupied by the bromido ligand (Figure 5).
In contrast, the imidazolyl N-atoms are not coordinated to
the metal center. The positions of the bromido ligand and
the carbonyl ligand C(3)O(3) in trans position are disor-
dered with an occupancy of 70:30. As shown in Figure 5,
the NH functionalities of both imidazolyl rings form intra-
and intermolecular hydrogen bonds in the solid state.
Partition Coefficient and CO Release Study
The distribution of drugs in different organs and tissues
is mainly determined by the lipophilic/hydrophilic nature of
these compounds. Thus, the n-octanol/water partition coef-
ficient logD was determined at pH = 7.4 by the “shake-
flask” method to assess the bioavailability of complexes 1–
Figure 3. Solid-state structure of 4a·H2O·(CH3)2CO. Both solvate
molecules, the counterion, and nonacidic H atoms are omitted for
clarity. Displacement ellipsoids are drawn at the 50% level.
6 (Table 3).[43] Compared to cisplatin, for which logD7.4
=
–2.53Ϯ0.28 was determined,[44] all of the new complexes
are more lipophilic, whereas no trend can be recognized in
relation to the substitution pattern of the ligands. However,
we observed an unexpected reversal of hydrophilicity be-
tween the 2-TIPH and 2-TIPNMe complexes.
Table 3. n-Octanol/water partition coefficient logD7.4 of com-
pounds 1–6, amount of ligand exchange after 24 h in competition
with HisOMe, and number of CO equiv. released per mol of com-
plex.
Complex
logD7.4
Ligand exchange n(CO) released
1a
2a
3a
4a
1b
2b
3b
4b
5b
6
1.59Ϯ0.06
0.46Ϯ0.02
1.34Ϯ0.04
1.86Ϯ0.10
0.79Ϯ0.03
–0.16Ϯ0.02
1.48Ϯ0.06
1.27Ϯ0.04
2.02Ϯ0.12
1.35Ϯ0.03
not observed
not observed
not observed
not observed
n.d.
4.5%
21.9%
n.d.
23.1%
n.d.
n.d.[a]
n.d.
n.d.
n.d.
1.82Ϯ0.05
1.83Ϯ0.26
0.83Ϯ0.09
0.96Ϯ0.01
1.32Ϯ0.21
n.d.
Figure 4. Solid-state structure of 5b·(C2H5)2O. The diethyl ether
solvate molecule, the counterion, and nonacidic H atoms are omit-
ted for clarity. Displacement ellipsoids are drawn at the 50% level.
[a] n.d.: not determined.
Another critical requirement for compounds intended for
use in diagnostic and/or therapeutic applications is the in-
ertness under physiological conditions. In particular, the
heavier group 7 transition metal isotopes 99mTc and
186/188Re can be used for imaging and therapeutic purposes,
respectively, because of their favorable nuclear properties
(
99mTc: t1/2 = 6 h, Eγ = 140 keV; 188Re: t1/2 = 19.6 h, Eγ =
2.1 MeV; 186Re: t1/2 = 88.9 h, Eγ = 1.09 MeV).[45] Typically,
99mTc radiopharmaceuticals clear the body within 24 h. In
order to mimic the physiological challenges under such con-
Figure 5. Solid-state structure of 6. Intra- and intermolecular H-
bonds are indicated by dashed lines and nonacidic H-atoms are
omitted for clarity. Br(1) and C(3)O(3) show a positional disorder; ditions, compounds 1a–5a, 2b, 3b, and 5b were incubated
only one orientation is shown. Displacement ellipsoids are drawn
at the 50% level. Selected bond lengths [Å] and angles [°]: Re(1)–
P(1) 2.4896(8), Re(1)–P(2) 2.5170(9), Re(1)–Br(1) 2.6169(8), Re(1)–
Br(1B) 2.563(2), Re(1)–C(1) 1.934(4), Re(1)–C(2) 1.933(4), Re(1)–
at 1 m with a 10 m solution of histidine methyl ester
(HisOMe) in [D6]dmso for 24 h and spectral changes moni-
1
tored by H and 31P{1H} NMR spectroscopy. No ligand
exchange could be observed in these experiments for the
carbonylrhenium compounds 1a–4a, which highlights the
promising properties of these compounds for the develop-
ment of M(CO)3-based radiopharmaceuticals. The corre-
sponding manganese compounds are not as inert as the rhe-
nium analogues. After 2 h, a new signal is observed in the
C(3) 1.911(7), Re(1)–C(3B) 1.919(14), C(1)–O(1) 1.144(5), C(2)–
O(2) 1.149(5), C(3)–O(3) 1.183(8), C(3B)–O(3B) 1.172(16); P(1)–
Re(1)–Br(1) 86.98(3), P(1)–Re(1)–Br(1B) 89.49(6), P(2)–Re(1)–
Br(1) 99.37(3), P(2)–Re(1)–Br(1B) 90.98(5), P(1)–Re(1)–P(2)
99.67(3), C(2)–Re(1)–C(1) 85.35(18), C(3)–Re(1)–C(1) 94.0(2),
C(3B)–Re(1)–P(1) 88.3(4), C(3)–Re(1)–C(2) 90.8(2), C(3B)–Re(1)–
C(2) 87.9(5).
Eur. J. Inorg. Chem. 2009, 5358–5366
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5361

P. C. Kunz, W. Huber, A. Rojas, U. Schatzschneider, B. Spingler
FULL PAPER
31P{1H} spectra of 2b, 3b, and 5b, and after 24 h about 5% leased, which is also usually found in other complexes
of the 2-TIPNMe complex 2b and 20–25% of the 4-TIPiPr LMn(CO)3.[46,47] Apparently, the intermediates formed af-
and 4-TIPSiPr complexes 3b and 5b have decomposed.
ter liberation of the first carbon monoxide have a different
To study the suitability of the compounds to act as novel reactivity towards further photolytic release of the remain-
CO-releasing molecules (CORMs), the manganese com- ing CO ligands depending on the TIP ligand. The electronic
plexes 1b–5b of the general formula [LMn(CO)3]+ (L = 4- and steric effects that govern this behavior will be the sub-
TIPOiPr, 4-TIPSiPr, 4-TIPiPr, and 2-TIPNMe) were investi- ject of a more detailed study involving time-resolved spec-
gated by using the UV/Vis-based myoglobin (Mb) assay.[14] troscopic investigation of 1b–5b and electronic structure
The rhenium complexes do not show any significant ab- calculations on the title compounds and their photoprod-
sorption above 320 nm and are thus not suitable as photo- ucts.
activatable CORMs. Changes in the UV/Vis spectra of re-
duced MbFeII in phosphate buffer in the presence of the
metal complexes with and without irradiation at 365 nm
were monitored for an extended period of time. In the ab-
sence of light, no spectral changes were observed over 1
to 2 h, indicating that complexes 1b–5b do not release CO
spontaneously in aqueous solution in the dark. In contrast,
Figure 6 shows the evolution of the spectral features of a
mixture of reduced MbFeII in PBS buffer after addition of
[(2-TIPNMe)Mn(CO)3]OTf (2b) and subsequent irradiation
at 365 nm. The intensity of the Q-band of MbFe at 557 nm
slowly decreases, while the typical signature of the
MbFeCO adduct appears at 540 and 577 nm. The concen-
tration of MbFeCO can be determined from the absorption
data by using ε540 nm(MbFeCO) = 15.4 mmol–1 Lcm–1 and
applying Lambert-Beer’s law. Figure 7 shows the change in
absorption at different wavelengths as a function of the irra-
diation time. Under the conditions employed, photolytic
upon radiation at 365 nm of a solution of reduced horse skeletal
Figure 7. Change of absorption at 540, 557, and 577 nm with time
muscle myoglobin (70 µ) and [(2-TIPNMe)Mn(CO)3]OTf (2b,
20 µ) in 0.1  phosphate buffer.
CO release is complete after about 60 min, when all of the
complex has been decomposed, as myoglobin was used in
excess. In Table 3, the number of CO equiv. released per
mol of complex is shown. Interestingly, the substitution
pattern of the imidazolyl ligand seems to determine the
number of CO equiv. released per mol of complex. Whereas
compounds 1b and 2b with the imidazol-2-ylphosphane li-
Conclusions
Ten new Re- and Mn(CO)3 complexes with imidazolyl-
gand liberate approximately 2 mol of CO per mol of com- phosphane ligands have been prepared and fully charac-
plex, in 3b–5b with the coordinated imidazol-4-ylphos- terized, including X-ray structure analysis for a number of
phanes, only one molecule of CO per Mn(CO)3 unit is re- compounds. In the case of the P=E complexes with E = O
or S, exclusive N,N,N-coordination of the tripodal ligands
was observed, whereas if only P- and N-coordination can
compete, the former is preferred. The Re complexes of the
tripodal ligands were inert towards ligand exchange with
histidine in a challenge experiment and all complexes dis-
played logD values at physiological pH, which indicated
potentially good bioavailability. CO-release investigations
of the Mn complexes with the myoglobin assay show that
these complexes act as photoinducible CO-releasing mole-
cules (CORMs) upon UV radiation, while they are stable
towards decomposition and do not liberate CO spontane-
ously in the absence of light, even in aqueous solution. The
substitution pattern of the imidazolylphosphane ligand was
found to determine the number of CO molecules released.
Whereas the compounds with the imidazol-2-ylphosphane
liberate approximately 2 mol of CO per mol of complex,
those with the imidazol-4-ylphosphane release only 1 mol
Figure 6. UV/Vis spectral changes in the Q-band region of a solu-
of CO per Mn(CO)3 unit. Further work will be directed
tion of reduced horse skeletal muscle myoglobin (70 µ) and [(2-
TIPNMe)Mn(CO)3]OTf (2b, 20 µ) in 0.1  phosphate buffer upon
irradiation at 365 nm (t = 0–150 min).
towards additional functionalization of these ligands, for
example by conjugation to biomolecules or macromolecular
5362
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2009, 5358–5366

MnI- and ReI(CO)3 Complexes of Imidazol-Based Phosphane Ligands
tated solid was washed with acetone to yield the product as a white
solid. Yield: 129 mg (84%). H NMR (200 MHz, [D4]methanol): δ
delivery systems as well as the modification of the tris(imid-
azolyl)phosphane ligands to alter the CO liberation charac-
teristics. Also, a detailed time-resolved spectroscopic and
theoretical study of the primary photoproducts will be car-
ried out to elucidate the factors that govern the different
CO release properties.
1
= 4.08 (s, 9 H, NCH3), 7.46 (dd, J = 1.0, J = 4.0 Hz, 3 H, Him),
7.67 (d, J = 1.0 Hz, 3 H, Him) ppm. 31P{1H} NMR (81 MHz, [D4]-
methanol): δ = –113.5 (s) ppm. ESI-MS (MeOH): m/z (%) = 545
(62) [M]+, 535 (57) [M – O – CO]+, 517 (16) [M – CO]+, 489 (15)
[M – 2 CO]+, 479 (100) [M – oxide – 3 CO]+, 461 (96) [M – 3
CO]+. C15H15BrN6O3PRe·H2O (642.42): calcd. C 28.04, H 2.67, N
13.08; found C 27.79, H 2.36, N 12.86. IR (KBr): ν = 2007 (s),
˜
1886 (vs) cm–1.
Experimental Section
[(4-TIPiPr)Re(CO)3]Br (3a): In a Schlenk tube, 4-TIPiPr (22 mg,
0.062 mmol) and [Re(H2O)3(CO)3]Br (25 mg, 0.062 mmol) were
dissolved in methanol (20 mL). The solution was stirred at reflux
for 2 h. After this time, the solvent was evaporated, and the residue
was washed with acetone to give a white solid product. Yield:
General: All reactions were carried out in Schlenk tubes under dry
nitrogen by using anhydrous solvents purified according to stan-
dard procedures. The metal complexes could be prepared by using
nondried solvents. All chemicals were purchased from commercial
sources and used as received. 1H and 31P NMR spectra were re-
1
1
22 mg (50%). H NMR (200 MHz, [D4]methanol): δ = 1.42 [d, J
corded with a Bruker DRX 200 spectrometer. The H NMR spec-
= 7.0 Hz, 18 H, CH(CH3)2], 3.90 [sept, J = 7.0 Hz, 3 H, CH(CH3)
2], 7.62 (d, J = 2.0 Hz, 3 H, Him) ppm. 31P{1H} NMR (81 MHz,
[D4]methanol): δ = 101.4 (s) ppm. ESI-MS (MeOH/H2O): m/z (%)
= 629.4 (100) [M]+, 645.4 (35) [M + O]+, 601.4 (34) [M – CO]+,
410.3 (56) [M – 2 (C6N2H9)]+. C21H27BrN6O3PRe·0.5H2O (717.57):
calcd. C 35.15, H 3.93, N 11.71; found C 34.89, H 3.54, N 11.47.
tra were calibrated against the residual proton signal of the solvent
as an internal reference ([D1]chloroform: δH = 7.30 ppm; [D4]meth-
anol: δH = 5.84 ppm; [D6]acetone: δH = 2.05 ppm), whereas the
31P{1H} NMR spectra were referenced to external 85% H3PO4.
The ESI mass spectra were recorded with a Finnigan LCQ Deca
ion trap API mass spectrometer. The MALDI mass spectra were
recorded with a Bruker Ultraflex MALDI-TOF mass spectrometer.
The FAB mass spectra were recorded with a Finnigan MAT 8200
mass spectrometer by using a nitrobenzyl alcohol (NBA) matrix.
Infrared spectra were recorded with a Bruker IFS 66 FTIR spec-
trometer. The elemental composition of the compounds was deter-
mined with a Perkin–Elmer Analysator 2400 at the Institut für
Pharmazeutische und Medizinische Chemie, Heinrich-Heine Uni-
versität Düsseldorf.
IR (KBr): ν = 2021 (s), 1902 (vs) cm–1.
˜
[(4-TIPOiPr)Re(CO)3]Br
(4a):
[Re(CO)3(H2O)3]Br
(50 mg,
0.12 mmol) and 4-TIPOiPr (48 mg, 0.12 mmol) were dissolved in
methanol (30 mL) and heated to reflux for 3 h. The reaction mix-
ture was then concentrated to 5 mL, and diethyl ether (30 mL) was
added. The suspension was stored at 0 °C overnight. After fil-
tration, the precipitated solid was washed with diethyl ether and
dried in vacuo to yield 43 mg (50%) of a white solid. Crystals suit-
able for X-ray single-crystal analysis were obtained by slow evapo-
: In a
4-TIPSiPr 100-mL Schlenk flask, 4-TIPiPr[23] (500 mg,
1
ration of a water/acetone solution. H NMR (200 MHz, [D4]meth-
1.39 mmol) was dissolved in ethanol (10 mL). Elemental sulfur
(134 mg, 4.18 mmol) was added to this solution and the reaction
mixture stirred at ambient temperature overnight. The resulting
white suspension was filtered, and the white solid that precipitated
was washed with carbon disulfide and diethyl ether and then dried
anol): δ = 1.42 [d, J = 7 Hz, 18 H, CH(CH3)2], 3.90 [sept, J =
7.0 Hz, 3 H, CH(CH3)2], 7.62 (d, J = 2.0 Hz, 3 H, Him) ppm.
31P{1H} NMR (81 MHz, [D4]methanol): δ = 3.0 (s) ppm. ESI-MS
(MeOH/H2O): m/z (%) = 629.4 (100) [M]+, 645.4 (35) [M + O]+,
– – 2
CO]+, 410.3 (56) [M (C6N2H9)]+.
1
601.4 (34) [M
C21H27BrN6O3PRe·0.5H2O (717.57): calcd. C 35.15, H 3.93, N
in vacuo. Yield 0.46 g (85%). H NMR (200 MHz, [D4]methanol):
δ = 1.33 [d, J = 7.0 Hz, 18 H, CH(CH3)2], 3.13 [sept, J = 7.0 Hz,
3 H, CH(CH3)2], 7.42 (d, JPH = 2.0 Hz, 3 H, Him) ppm. 31P{1H}
NMR (81 MHz, [D4]methanol): δ = 1.0 (s) ppm. FAB+-MS (NBA):
11.71; found C 34.89, H 3.54, N 11.47. IR (KBr): ν = 2021 (s),
˜
1902 (vs) cm–1.
m/z (%)
= –
390 (731) [M]+, 249 (100) [M S-imiPr]+.
[(4-TIPSiPr)Re(CO)3]Br
(5a):
[Re(CO)3(H2O)3]Br
(50 mg,
C18H27N6PS·0.5H2O (399.50): calcd. C 54.41, H 7.06, N 21.04;
found C 54.60, H 7.28, N 20.90.
0.12 mmol) and 4-TIPSiPr (48 mg, 0.12 mmol) were dissolved in
methanol (30 mL) and heated to reflux for 2 h. The reaction mix-
ture was concentrated to 5 mL, and diethyl ether (30 mL) was
added. The suspension was stored at 0 °C overnight. After fil-
tration, the solid was washed with diethyl ether and dried in vacuo.
The product still contained a small amount of 4a, as determined
[(2-TIPH)Re(CO)3]Br (1a): In a Schlenk tube, 2-TIPH (58 mg,
0.25 mmol) and [Re(H2O)3(CO)3]Br (100 mg, 0.25 mmol) were dis-
solved in methanol (20 mL). The solution was stirred at reflux for
5 h. Then the solution was concentrated to 3 mL, and water
(20 mL) was added. The precipitated white solid was filtered off
and washed with water. The residue was redissolved in methanol,
precipitated with n-hexane and dried in vacuo to obtain the prod-
uct as a white solid. Yield 93 mg (144 mg) (65%). 1H NMR
(200 MHz, [D4]methanol): δ = 7.22 (dd, J = 1.0, J = 2.7 Hz, 3 H,
Him), 7.58 (d, J = 1.0 Hz, 3 H, Him) ppm. 31P{1H} NMR (81 MHz,
[D4]methanol): δ = –99.2 (s) ppm. FAB+-MS (NBA): m/z (%) =
503 (77) [M]+, 475 (10) [M – CO]+. C12H9BrN6O3PRe·5/3hexane
(725.66): calcd. C 29.55, H 2.77, N 13.25; found C 29.48, H 2.73,
1
by NMR spectroscopy. Yield: 35 mg (39%). H NMR (200 MHz,
[D6]dmso): δ = 1.31 [d, J = 7.0 Hz, 6 H, CH(CH3)2], 1.38 [d, J =
7.0 Hz, 6 H, CH(CH3)2], 1.43 [d, J = 7.0 Hz, 6 H, CH(CH3)2], 7.97
(s, 2 H, Him), 8.70 (d, J = 2.5 Hz, 1 H, Him), 13.37 (br. s, 1 H, NH),
13.71, (br. s, 2 H, NH) ppm. 31P{1H} NMR (81 MHz, [D6]dmso):
δ = –3.4 (s) ppm. ESI-MS (CH3OH/HCOOH): m/z (%) = 661.4
(100) [(4-TIPSiPr)Re(CO)3]+, 645.4 (20) [(4-TIPOiPr)Re(CO)3]+,
603.4 (28) [(4-TIPSiPr)Re(CO)]+. IR (KBr): ν = 2029 (s), 1908 (vs)
˜
cm–1.
N 13.09. IR (KBr): ν = 2025 (s), 1898 (vs) cm–1.
˜
Synthesis of [LMn(CO)3]OTf Complexes 1b–5b: In a Schlenk tube,
pentacarbonylmanganese bromide (100 mg, 0.36 mmol) and silver
triflate (93.5 mg, 0.36 mmol) were dissolved in anhydrous acetone
(20 mL). After heating to reflux for 1.5 h, the precipitated silver
bromide was filtered off and the clear yellow solution added to
an acetone solution of the respective ligand (0.36 mmol). Further
[(2-TIPNMe)Re(CO)3]Br (2a): In a Schlenk tube, 2-TIPNMe (69 mg,
0.25 mmol) and [Re(H2O)3(CO)3]Br (100 mg, 0.25 mmol) were dis-
solved in methanol (15 mL). The solution was stirred at reflux for
3.5 h and then concentrated to 5 mL. Diethyl ether (25 mL) was
added and the suspension stored at 0 °C overnight. The precipi-
Eur. J. Inorg. Chem. 2009, 5358–5366
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
5363

P. C. Kunz, W. Huber, A. Rojas, U. Schatzschneider, B. Spingler
(682.6): calcd. C 38.83, H 4.30, N 12.35; found C 38.77, H 4.80, N
FULL PAPER
heating to reflux for 1.5 h led to formation of the product, which
either precipitated directly from the reaction solution (7) or precipi-
tated after reducing the volume of the reaction solution to 5 mL
and adding diethyl ether. After filtration, the solid product was
washed with diethyl ether and dried in vacuo.
12.10. IR (KBr): ν = 2031 (s), 1935 (vs) cm–1.
˜
[(4-TIPSiPr)Mn(CO)3]OTf (5b): Crystals were obtained by slow dif-
fusion of diethyl ether into a methanol solution of 5b. Yield:
1
153 mg (63%). H NMR (200 MHz, [D6]acetone): δ = 1.43 [d, J =
[(2-TIPH)Mn(CO)3]OTf (1b): Yield: 84 mg (42%). 1H NMR
(200 MHz, [D4]methanol): δ = 7.32 (br. s, 3 H, Him), 7.68 (br. s, 3
H, Him) ppm. 31P{1H} NMR (81 MHz, [D4]methanol): δ = –101.7
ppm. ESI-MS (CH3OH/H2O): m/z (%) = 371.1 (29) [M]+, 315.1 (7)
7.0 Hz, 18 H, CH(CH3)2], 3.94 [sept, J = 7.0 Hz, 3 H, CH(CH3)2],
7.90 (s, 3 H, Him) ppm. 31P{1H} NMR (81 MHz, [D6]acetone): δ
= –7.0 (s) ppm. ESI-MS (CH3OH/H2O): m/z (%) = 529.2 (17)
[M]+, 473.0 (13) [M – 2 CO]+, 445.2 (100) [M – 3 CO]+.
C22H27F3MnN6O6PS2·CH3OH (710.6): calcd. C 38.88, H 4.40, N
[M – 2 CO]+, 287.1 (100) [M – 3CO]+. IR (KBr): ν = 2041 (s),
˜
1915 (vs) cm–1. C13H9F3MnN6O6PS·H2O·CH3OH (567.0): calcd. C
11.83; found C 39.34, H 4.26, N 11.82. IR (KBr): ν = 2032 (s),
˜
1929 (vs) cm–1.
29.49, H 2.65, N 14.74; found C 29.55, H 2.31, N 14.56.
[(2-TIPNMe)Mn(CO)3]OTf (2b): Yield: 138 mg (61%). 1H NMR
[(4-MIPiPr)2BrRe(CO)3] (6): In a Schlenk tube, [Re(H2O)3(CO)3]Br
(100 mg, 0.25 mmol) and 4-MIPiPr (146 mg, 0.5 mmol) were dis-
solved in methanol (20 mL). The solution was stirred at reflux for
3 h. The reaction mixture was then concentrated to 5 mL, and, af-
ter 48 h at ambient temperature, a colorless solid had precipitated.
This was filtered off and washed with methanol to afford a white
(200 MHz, [D4]methanol): δ = 4.01 (s, 9 H, NCH3), 7.38 (d, JPH
=
4.0 Hz, 3 H, Him), 7.66 (s, 3 H, Him) ppm. 31P{1H} NMR (81 MHz,
[D4]methanol): δ = –115.7 (s) ppm. ESI-MS (CH3OH): m/z (%) =
401.2 (7) [M – CO + O]+, 345.7 (11) [M – 3 CO + O]+, 329.2 (100)
[M – 3 CO]+. C16H15F3MnN6O6PS·H2O (580.3): calcd. C 33.12, H
1
2.95, N 14.48; found C 33.55, H 2.70, N 14.67. IR (KBr): ν = 2033
˜
solid product. Yield: 53 mg (23%). H NMR (200 MHz, [D1]chlo-
(s), 1919 (vs) cm–1.
roform): δ = 1.32 [d, J = 7.0 Hz, 12 H, CH(CH3)2], 2.99 [sept, J =
7.0 Hz, 2 H, CH(CH3)2], 6.55 (d, J = 1.0 Hz, 2 H, Him), 7.27 (m,
20 H, Ph), 11.06 (s, 2 H, NH) ppm. 31P{1H} NMR (81 MHz, [D1]-
chloroform): δ = –16.0 ppm. MALDI-MS (CHCl3): m/z (%) =
911.2 (76) [M – CO + H]+, 882.2 (51) [M – 2 CO + H]+, 859.3 (60)
[M – Br]+, 831.3 (100) [M – CO – Br]+. FAB+-MS (NBA): m/z (%)
= 859.4 (73) [M – Br]+, 831.4 (36) [M – CO – Br]+, 802.3 (3.3) [M –
2 CO – Br]+, 565.1 (22) [M – (4-MIPiPr) – Br]+, 509.2 (19) [M – (4-
MIPiPr) – CO – Br]+. C39H38BrN4O3P2Re (938.81): calcd. C 49.9,
[(4-TIPiPr)Mn(CO)3]OTf (3b): Yield: 197 mg (84%). 1H NMR
(200 MHz, [D4]methanol): δ = 1.44 [d, J = 7.0 Hz, 18 H, CH-
(CH3)2], 3.91 [sept, J = 7.0 Hz, 3 H, CH(CH3)2], 7.55 (d, J =
2.0 Hz, 3 H, Him) ppm. 31P{1H} NMR (81 MHz, [D4]methanol): δ
= –103.6 (s) ppm. ESI-MS (CH3OH): m/z (%) = 497.2 (5) [M]+,
441.3 (4) [M
–
2
CO]+, 413.3 (100) [M
–
3
CO]+.
C22H27F3MnN6O6PS (646.5): calcd. C 40.87, H 4.21, N 13.00;
found C 40.94, H 4.38, N 12.77. IR (KBr): ν = 2027 (s), 1933 (vs)
˜
cm–1.
H 4.08, N 5.97; found C 49.55, H 3.87, N 5.92. IR (KBr): ν =
˜
2031, 1948, 1920 cm–1.
[(4-TIPOiPr)Mn(CO)3]OTf (4b): Yield: 162 mg (67%). 1H NMR
(200 MHz, [D4]methanol): δ = 1.45 [d, J = 7.0 Hz, 18 H, CH- Partition Coefficients (logD): The n-octanol/water partition coeffi-
(CH3)2], 3.87 [sept, J = 7.0 Hz, 3 H, CH(CH3)2], 7.81 (s, 3 H, Him
)
cient of compounds 1–6 was determined by using the shake-flask
method. PBS-buffered bidistilled water [100 mL, phosphate buffer,
ppm. 31P{1H} NMR (81 MHz, [D4]methanol): δ = 1.3 (s) ppm.
ESI-MS (CH3OH/H2O): m/z (%) = 513.2 (22) [M]+, 457.1 (16) [M – c(PO43–) = 10 m, c(NaCl) = 15 , pH adjusted to 7.4 with hydro-
2 CO]+, 429.3 (100) [M – 3 CO]+. C22H27F3MnN6O7PS·H2O
chloric acid] and n-octanol (100 mL) were shaken together by using
Table 4. Crystallographic data of 2b, 2b·(CH3)2CO, 4a·H2O·(CH3)2CO, 5b·Et2O, and 6.
2b
2b·(CH3)2CO
4a·H2O·(CH3)2CO
5b·Et2O
6
Empirical formula
M [gmol–1]
C16H15F3MnN6O6PS
562.31
C19H21F3MnN6O7PS
620.39
C25H35F3N6O9PReS
869.82
C26H37F3MnN6O7PS2
752.65
C39H38BrN4O3P2Re
938.78
Diffractometer
Oxford Excalibur, Ruby
CCD detector
Oxford Excalibur, Ruby
CCD detector
Stoe IPDS
Stoe IPDS
Oxford Excalibur, Ruby
CCD
detector
T [K]
183(2)
183(2)
183(2)
183(2)
183(2)
Crystal system
Space group
monoclinic
P21/c
triclinic
P1
triclinic
P1
orthorhombic
Pnma
monoclinic
P21/c
¯
¯
a [Å]
b [Å]
c [Å]
α [°]
10.4537(4)
13.1812(5)
16.0452(7)
8.0165(3)
11.7299(6)
14.9909(6)
86.923(4)
79.851(4)
74.991(4)
1340.1(1)
2
9.6736(9)
12.2041(11)
16.3861(13)
76.03(1)
76.10(1)
69.73(1)
1734.7(3)
2
17.1900(8)
12.7363(7)
16.0560(7)
9.58994(6)
19.50377(11)
20.82476(13)
β [°]
92.067(3)
96.2878(6)
γ [°]
V [Å3]
2209.47(15)
4
1.690
3515.3(3)
4
1.422
3871.63(4)
4
1.611
Z
Dcalcd. [Mgm–3]
1.537
0.700
1.665
3.680
µ/mm–1
0.837
0.605
4.295
Reflections collected
Independent reflections
21758
6729 [0.0439]
13206
6656 [0.0380]
20765
7129 [0.0803]
31823
4208 [0.1016]
118629
11815 [0.0357]
[Rint
]
Final R indices [I Ͼ 2σ(I)] R1 = 0.0522
wR2 = 0.1157
R1 = 0.0444
wR2 = 0.0662
R1 = 0.1098
wR2 = 0.0736
R1 = 0.0611
wR2 = 0.1484
R1 = 0.0697
wR2 = 0.1545
R1 = 0.0587
wR2 = 0.1460
R1 = 0.0735
wR2 = 0.1545
R1 = 0.0324
wR2 = 0.0752
R1 = 0.0439
wR2 = 0.0774
Final R indices (all data)
R1 = 0.0948
wR2 = 0.1228
5364
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2009, 5358–5366

MnI- and ReI(CO)3 Complexes of Imidazol-Based Phosphane Ligands
a laboratory shaker (Perkin–Elmer) for 72 h to allow saturation of
both phases. Each compound (1 mg) was mixed in aqueous and
organic phase (1 mL) for 10 min by using a laboratory vortexer.
The resulting emulsion was centrifuged (3000 g, 5 min) to separate
the phases. The concentrations of each complex in the aqueous and
organic phases were determined by using UV/Vis spectroscopy at
260 nm; logDpH was defined as the logarithm of the ratio of the
concentrations of the complex in the organic and aqueous phase
(logD = log{[complex(org)]/[complex](aq)}); the value reported is the
mean of three separate determinations.
Prof. Dr. Nils Metzler-Nolte and P. C. K. thanks Prof. Dr. Wolf-
gang Kläui for generous access to all facilities of the institutes.
[1] B. E. Mann, R. Motterlini, Chem. Commun. 2007, 4197.
[2] L. Wu, R. Wang, Pharmacol. Rev. 2005, 57, 585.
[3] S. W. Ryter, J. Alam, A. M. K. Choi, Physiol. Rev. 2006, 86,
583.
[4] M. Vadori, M. Seveso, F. Besenzon, E. Bosio, E. Tognato, F.
Fante, M. Boldrin, S. Gavasso, L. Ravarotto, B. Mann, P. Si-
mioni, E. Ancona, R. Motterlini, E. Cozzi, Xenotransplantation
2009, 16, 99.
CO-Release Studies: All UV/Vis measurements were performed
with a Jasco V-670 spectrophotometer at room temperature in a
quartz cuvette (d = 1 cm). Horse skeletal muscle myoglobin (Fluka)
was dissolved in 0.1  phosphate buffer pH = 7.3 and degassed by
bubbling with nitrogen. Then, it was reduced by the addition of an
excess of sodium dithionite in the same solvent, and finally buffer
was added to the cuvette to a total volume of 749 µL. To this solu-
tion, complex (1 µL) dissolved in dimethyl sulfoxide was added to
give a final concentration of 20 µmolL–1 of metal complex and
75 µmolL–1 of myoglobin with A(557 nm) Ͻ 1. Solutions were then
either kept in the dark or irradiated for given time intervals under
nitrogen at 365 nm with a UV hand lamp positioned perpendicular
to the cuvette at a distance of 6 cm. Irradiations were interrupted
at regular intervals to take UV/Vis spectra. All measurements were
carried out in triplicate to analyze the reproducibility of the CO
release.
[5] E. Stagni, M. Privitera, C. Bucolo, G. Leggio, R. Motterlini,
F. Drago, Br. J. Ophthalmol. 2009, 93, 254.
[6] S. Chlopicki, R. Olszanecki, E. Marcinkiewicz, M. Lomnicka,
R. Motterlini, Cardiovasc. Res. 2006, 71, 393.
[7] R. Alberto, R. Motterlini, Dalton Trans. 2007, 1651.
[8] T. R. Johnson, B. E. Mann, R. Foresti, R. Motterlini, Circ.
Res. 2003, 42, 3722.
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Drugs 2005, 14, 1305.
[10] J. E. Clark, P. Naughton, S. Shurey, C. J. Green, T. R. Johnson,
B. E. Mann, R. Foresti, R. Motterlini, Circ. Res. 2003, 93, e2.
[11] I. J. S. Fairlamb, J. M. Lynam, B. E. Moulton, I. E. Taylor,
A. K. Duhme-Klair, P. Sawle, R. Motterlini, Dalton Trans.
2007, 3603.
[12] P. Sawle, J. Hammad, I. J. S. Fairlamb, B. Moulton, C. T.
O’Brien, J. M. Lynam, A. K. Duhme-Klair, R. Foresti, R.
Motterlini, J. Pharmacol. Exp. Ther. 2006, 318, 403.
[13] I. J. S. Fairlamb, A.-K. Duhme-Klair, J. M. Lynam, B. E.
Moulton, C. T. O’Brien, P. Sawle, J. Hammad, R. Motterlini,
Bioorg. Med. Chem. Lett. 2006, 16, 995.
[14] R. Motterlini, J. E. Clark, R. Foresti, P. Sarathchandra, B. E.
Mann, C. J. Green, Circ. Res. 2002, 90, e17.
[15] J. Niesel, A. Pinto, H. W. Peindy N’Dongo, K. Merz, I. Ott, R.
Gust, U. Schatzschneider, Chem. Commun. 2008, 4292.
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Trans. 2009, 4292.
Crystallography: Crystallographic data were collected at 183(2) K
with Mo-Kα radiation (λ = 0.7107 Å) that was graphite-monochro-
mated. Suitable crystals were covered with oil (Infineum V8512,
formerly known as Paratone N), mounted on top of a glass fiber,
and immediately transferred to the diffractometer. The crystals
were measured either with a Stoe IPDS diffractometer [for
4a·H2O·(CH3)2CO and 5b·Et2O] or an Oxford Diffraction Xcalibur
system with a Ruby detector [for 2b, 2b·(CH3)2CO, and 6] (Table 4).
In the case of the IPDS, a maximum of 8000 reflections distributed
over the whole limiting sphere were selected by the program SE-
LECT and used for unit-cell parameter refinement with the pro-
gram CELL.[48] Data were corrected for Lorentz and polarization
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Acknowledgments
Part of this work was supported by the Deutsche Forschungsge-
meinschaft (DFG) within FOR 630 (“Biological function of orga-
nometallic compounds”) and the Fonds der Chemischen Industrie
(FCI). A. R. thanks the Deutscher Akademischer Austauschdienst
(DAAD) for an International Association for the Exchange of Stu-
dents for Technical Experience (IAESTE) fellowship. U. S. thanks
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Received: July 10, 2009
Published Online: November 4, 2009
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