Catalytic and anticancer activities of sawhorse-type diruthenium tetracarbonyl complexes derived from fluorinated fatty acids

Article abstract of DOI:10.1080/00958972.2013.790020

The reaction of fluorinated fatty acids, perfluorobutyric acid (C ₃F₇CO₂H), and perfluorododecanoic acid (C ₁₁F2₃CO₂H), with dodecacarbonyltriruthenium (Ru₃(CO)1₂) und

Full text of DOI:10.1080/00958972.2013.790020

Journal of Coordination Chemistry
ISSN: 0095-8972 (Print) 1029-0389 (Online) Journal homepage: http://www.tandfonline.com/loi/gcoo20
Catalytic and anticancer activities of sawhorse-
type diruthenium tetracarbonyl complexes
derived from fluorinated fatty acids
Justin P. Johnpeter , Laurent Plasseraud , Frédéric Schmitt , Lucienne
Juillerat-Jeanneret & Bruno Therrien
To cite this article: Justin P. Johnpeter , Laurent Plasseraud , Frédéric Schmitt , Lucienne
Juillerat-Jeanneret & Bruno Therrien (2013) Catalytic and anticancer activities of sawhorse-
type diruthenium tetracarbonyl complexes derived from fluorinated fatty acids, Journal of
Coordination Chemistry, 66:10, 1753-1762, DOI: 10.1080/00958972.2013.790020
To link to this article: http://dx.doi.org/10.1080/00958972.2013.790020
Accepted author version posted online: 26
Mar 2013.
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Date: 09 March 2016, At: 04:23

Journal of Coordination Chemistry, 2013
Vol. 66, No. 10, 1753–1762, http://dx.doi.org/10.1080/00958972.2013.790020
Catalytic and anticancer activities of sawhorse-type
diruthenium tetracarbonyl complexes derived from
fluorinated fatty acids
JUSTIN P. JOHNPETER†, LAURENT PLASSERAUD‡, FRÉDÉRIC SCHMITT§,
LUCIENNE JUILLERAT-JEANNERET§ and BRUNO THERRIEN*†
†Institut de Chimie, Université de Neuchâtel, Neuchâtel, Switzerland
‡Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR CNRS 6302, Dijon
Cedex, France
§Institut Universitaire de Pathologie, CHUV, Lausanne, Switzerland
(Received 30 January 2013; in final form 8 March 2013)
The reaction of fluorinated fatty acids, perfluorobutyric acid (C3F7CO2H), and perfluorododecanoic
acid (C11F23CO2H), with dodecacarbonyltriruthenium (Ru3(CO)12) under reflux in tetrahydrofuran,
followed by addition of two-electron donors (L) such as pyridine, 1,3,5-triaza-7-phosphatricyclo
[3.3.1.1]decane, or triphenylphosphine, gives stable diruthenium complexes Ru2(CO)4(μ2-η2-
O2CC3F7)2(L)2 (1a, L= C5H5N; 1b, L= PTA; 1c, L= PPh3) and Ru2(CO)4(μ2-η2-O2CC11F23)2(L)2
(2a, L= C5H5N; 2b, L= PTA; 2c, L= PPh3). The catalytic activity of the complexes for hydrogena-
tion of styrene under supercritical carbon dioxide has been assessed and compared to the analogous
triphenylphosphine complexes with non-fluorinated carboxylato groups Ru2(CO)4(μ2-η2-
O2CC3H7)2(PPh3)2 (3) and Ru2(CO)4(μ2-η2-O2CC11H23)2(PPh3)2 (4). In addition, the cytotoxicities
of the fluorinated complexes 1 were also evaluated on several human cancer cell lines (A2780,
A549, Me300, HeLa). The complexes appear to be moderately cytotoxic, showing greater activity
on the Me300 melanoma cells. Single-crystal X-ray structure analyses of 1a and 3 show the typical
sawhorse-type arrangement of the diruthenium tetracarbonyl backbone with two bridging carboxyl-
ates and two terminal ligands occupying the axial positions.
Keywords: Dinuclear complexes; Carbonyl ligands; Fluorinated fatty acids; Carboxylato bridges;
Ruthenium; Supercritical carbon dioxide
1. Introduction
Supercritical carbon dioxide (scCO2) is an interesting reaction medium for homogenous
catalysis due to its inertness in most catalytic reactions. The scCO2 is abundant, non-toxic,
non-flammable, readily available, and inexpensive and thus considered to be one of the
best ecologically friendly alternatives to conventional solvents [1]. However, metal
complexes are in general poorly soluble in scCO2. This major obstacle has been overcome
by using fluorinated derivatives, which remarkably improved the solubility of metal
*Corresponding author. Email: bruno.therrien@unine.ch
Ó 2013 Taylor & Francis

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J.P. Johnpeter et al.
complexes in scCO2 [2]. These fluorinated derivatives have been tested for different
catalytic reactions such as hydrogenation, oxidation, and hydroformylation [2].
Carbon monoxide has been recognized as an important signaling molecule in mammals.
It is produced by oxidation of heme by heme oxygenase, and evidence has been found that
CO possesses anti-inflammatory, vasodilatory, anti-apoptotic, anti-proliferative, and anti-
hypoxia therapeutic effects [3]. Notably, among chemotherapeutic metals, ruthenium is
now considered one of the most promising chemotherapeutic agents because of its low
toxicity and ability to mimic iron in living systems [4]. Consequently, ruthenium carbonyl
complexes have attracted considerable attention, and the biological role of such complexes
has been investigated by several research groups [5].
Recently, we evaluated the potential of sawhorse-type diruthenium tetracarbonyl
complexes as biological agents [6]. First reported by Lewis and co-workers in 1969 [7],
sawhorse-type diruthenium tetracarbonyl complexes are quite robust and are known to
catalyze various reactions [8]. Herein, we report the synthesis of sawhorse-type complexes
containing carboxylates derived from saturated fluorinated fatty acids (perfluorobutyric
acid, perfluorododecanoic acid) with a variety of axial ligands (pyridine, 1,3,5-triaza-7-
phosphatricyclo[3.3.1.1]decane, triphenylphosphine). The complexes were tested as
catalysts for the hydrogenation of styrene under scCO2 conditions, and the anticancer
activities of the perfluorobutyric acid derivatives were evaluated on human cancer cell
lines A2780, Me300, A549 and HeLa.
2. Results and discussion
Dodecacarbonyltriruthenium (Ru3(CO)12) reacts with an excess of saturated fluorinated
fatty acids, perfluorobutyric acid (C3F7CO2H), or perfluorododecanoic acid (C11F23CO2H),
in THF under reflux and high pressure to yield a solution containing the THF intermedi-
ates Ru2(CO)4(μ2-η2-O2CC3F7)2(THF)2 and Ru2(CO)4(μ2-η2-O2CC11F23)2(THF)2, respec-
tively. These labile dinuclear THF intermediates further react with two-electron donors (L),
such as pyridine (NC5H5) (a), 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (PTA) (b), or
triphenylphosphine (PPh3) (c), to generate in reasonable yields the stable dinuclear com-
plexes Ru2(CO)4(μ2-η2-O2CC3F7)2(L)2 (1a, L= C5H5N; 1b, L= PTA; 1c, L= PPh3) and
Ru2(CO)4(μ2-η2-O2CC11F23)2(L)2 (2a, L= C5H5N; 2b, L= PTA; 2c, L= PPh3) (figure 1).
Figure 1. Molecular structures of the dinuclear complexes Ru2(CO)4(μ2-η2-O2CC3F7)2(L)2 (1) and Ru2(CO)4
(μ2-η2-O2CC11F23)2(L)2 (2).

Sawhorse-type diruthenium
1755
Figure 2. Molecular structures of the dinuclear complexes Ru2(CO)4(μ2-η2-O2CC3H7)2(PPh3)2 (3) and
Ru2(CO)4(μ2-η2-O2CC11H23)2(PPh3)2 (4).
The same synthetic method was used to prepare the parent complexes Ru2(CO)4(μ2-η2-
O2CC3H7)2(PPh3)2 (3) and Ru2(CO)4(μ2-η2-O2CC11H23)2(PPh3)2 (4), containing non-fluori-
nated alkyl chains and triphenylphosphine axial ligands (figure 2).
These sawhorse-type dinuclear tetracarbonyl complexes are air-stable yellow crystalline
powders and have been completely characterized by infrared, NMR, mass spectrometry,
and elemental analysis. All complexes exhibit in the ν(CO) region of their infrared spectrum
the characteristic three bands around 2000 cmÀ1 for the terminal carbonyl groups [8], and
the strong and broad band for symmetric and asymmetric ν(OCO) vibrations of the bridging
carboxylato groups around 1660 cmÀ1. In the non-fluorinated derivatives 3 and 4, this
asymmetric ν(OCO) vibration band is observed at 1560 cmÀ1. In 1 and 2, all 1H NMR
spectra show the expected resonances for the axial ligands. For example, in 1a and 2a, the
protons of the pyridines are at δ = 7.5, 7.9, and 8.6 ppm in a 2:1:2 integration, while for
the PTA complexes 1b and 2b two multiplets of equal integrations at 4.3 and 4.6 ppm are
observed. In 1c, 2c, 3, and 4, three multiplets are observed in the aromatic region for the
axial PPh3, while in 3 and 4 additional signals corresponding to the alkyl chains are also
observed. In the 19F NMR spectra of 1, three distinct signals are observed and easily
assigned, while for 2 several additional signals corresponding to CF2 groups appear
between À120 and À125 ppm. For 1b and 2b, sharp singlets are observed at δ ≈ À54 ppm
in their 31P{1H} NMR spectra, while in 1c, 2c, 3, and 4 a sharp singlet appears at δ ≈
15 ppm, both in accord with coordination of PTA and PPh3 in the axial positions of saw-
horse-type diruthenium tetracarbonyl complexes [9].
Crystals of 1a and 3 were obtained by slow diffusion of pentane into a dichloromethane
solution of the corresponding complex. The single-crystal structure analyses of 1a and 3
show the Ru2(CO)4 sawhorse backbone with two pyridines (1a) or triphenylphosphines (3)
in the axial positions and the carboxylato bridges in the equatorial positions (figure 3).
The Ru–Ru distances [1a: 2.694(1) Å, 3: 2.7477(5) Å] are in the range of a ruthenium–
ruthenium single bond, as observed in analogous complexes [9]. The OCO bond angles of
the carboxylato bridges [1a: 129.2(5)°, 3: 125.3(3)°] differ only slightly from those
observed in other Ru2(CO)4(μ2-η2-O2CR)2L2 complexes [9]. In 3, the Ru–P distance is
2.4524(8) Å, consistent with Ru–P distances observed in analogous complexes [9]. The
remaining structural parameters appear to be normal for this type of complex [8]. Selected
bond lengths and angles for 1a and 3 are listed in the caption of figure 3.

1756
J.P. Johnpeter et al.
Figure 3. ORTEP representation of 1a and 3 showing ellipsoids at the 35% probability level with hydrogens
omitted for clarity (symmetry code: i = Àx, y, ½Àz). Selected bond lengths (Å) and angles (°): 1a, Ru1–Ru1i
2.694(1), Ru1–N1 2.218(4), Ru1–O1 2.151(4), Ru1–O2 2.149(4), O1–C1–O2i 129.2(5), N1–Ru1–Ru1i 165.79
(13), O1–Ru1–O2 83.52(18); 3, Ru1–Ru1i 2.7477(5), Ru1–P1 2.4524(8), Ru1–O1 2.130(2), Ru1–O2 2.124(2),
O1–C1–O2i 125.3(3), P1–Ru1–Ru1i 163.97(2), O1–Ru1–O2 87.66(10).
2.1. Catalytic evaluation
Several studies have reported the use of sawhorse-type diruthenium tetracarbonyl com-
plexes as efficient catalysts for isomerization, hydrogenation, carbonylation, and coupling
reactions. This aspect of the chemistry of sawhorse-type ruthenium complexes has been
detailed in a recent review [8]. The preparation in good yields of such new complexes
containing carboxylate ligands derived from saturated fluorinated fatty acids has motivated
interest to evaluate their catalytic properties under supercritical conditions of carbon diox-
ide. Indeed, ligands modified with perfluoroalkyl ponytails are known to exhibit a great
CO2-philic character, and thus, they have been used to increase the solubility of homoge-
neous catalysts in scCO2 [10]. In this preliminary catalytic study, selected sawhorse-type
diruthenium complexes with short (1b and 1c) and long (2c) fluorinated alkyl chains were
considered as catalyst for the hydrogenation of styrene in scCO2 conditions (equation (1)),
and their activities were also compared with those obtained with non-fluorinated analogs
(3 and 4) and Ru3(CO)12.
Catalytic data are summarized in table 1. The sawhorse-type diruthenium complexes are
very poor catalysts for hydrogenation of styrene. The conversions of styrene into ethyl
benzene are always below 15% regardless of the length of the fluorinated alkyl chains and
the nature of the axial ligands (PPh3 axial ligands seem to be the most suitable). In
addition, the yield in ethyl benzene is not increased by supercritical conditions of carbon
dioxide (entries 2 and 4). The incorporation of fluorinated alkyl chains leads finally to a
moderate benefit. In previous studies, the addition of a co-solvent, such as methanol, has
been reported to be helpful for increasing the catalytic activity of transition metal catalysts
under scCO2 conditions [11]. Herein, for the same complex (1c), we only observe a weak
positive effect with the presence of methanol (entries 2 and 3). In fact, the best conversion

Sawhorse-type diruthenium
1757
Table 1. Hydrogenation of styrene under supercritical carbon dioxide conditions.
Entry
Catalyst
Medium
Conversion (%)
Product
a
b
1
2
3
4
5
6
7
8
3
1c
1c
1c
1b
4
2c
2c
H2 /CO2b
07
06
10
12
04
03
06
06
22
71
95
Ethyl benzene
Ethyl benzene
Ethyl benzene
Ethyl benzene
Ethyl benzene
Ethyl benzene
Ethyl benzene
Ethyl benzene
Ethyl benzene
Ethyl benzene
Ethyl benzene
H2a/CO2
H2aa/CO2b/CH3OHc
H2
H2a/CO2
b
H2a/CO2b/CH3OHc
H2aa/CO2b/CH3OHc
H2
b
9
10
11
Ru3(CO)12
Ru3(CO)12
recovery of entry 10
H2aa/CO2
H2a
H2
Reaction conditions: Amount of catalyst = 0.02 mmol, substrate/catalyst = 500, T = 65 °C, reaction time = 16 h.
b
c
aPH2 = 10 bar. Ptotal = 120 bar. 1 mL.
Table 2. Cytotoxicity of 1 after 72 h exposure of human cancer cells.
IC50 [μM]
Cell lines
HeLa
A549
Me300
A2780
1a
1b
1c
199
190
73
9
9
1
1
179
184
61
1
5
8
1
178
190
63
2
2
1
1
124
111
129
is obtained using Ru3(CO)12 as catalyst (entry 9). The conversion is further enhanced
when the reaction is only carried out in the presence of H2 (entries 10 and 11). However,
the degradation of the catalyst is also observed, leading to a final black precipitate sus-
pected to correspond to ruthenium nanoparticles [12]. Thus, the low activity recorded with
these sawhorse-type diruthenium tetracarbonyl complexes can be rationalized by the stabil-
ity and preservation of the starting ruthenium species in the scCO2 reaction medium.
2.2. Biological studies
The cytotoxicity of 1 was evaluated in vitro on human cancer cell lines: HeLa cervix, A549
pulmonary, Me300 melanoma, A2780 ovarian. Unfortunately, the poor solubility of 2, 3,
and 4 did not allow their assessment. Cells were exposed for 72 h to increasing
concentrations of 1a-1c, and their survival was determined using the MTT assay (MTT =
3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyltetrazolium bromide). In all cell lines, the
complexes show similar cytotoxicity with an IC50 ranging from 60 to 200 μM depending on
the cell line tested (table 2). These results suggest that the nature of the axial ligands plays
only a minor role on the overall cytotoxicity. Among the cell lines tested, Me300 melanoma
cells were the most sensitive cells to all complexes. This is important since melanoma
tumors are aggressive and resistant to common chemotherapeutic treatments [13].
3. Conclusion
A series of sawhorse-type complexes containing carboxylates derived from saturated
fluorinated fatty acids have been prepared and evaluated as catalysts for the hydrogenation of

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J.P. Johnpeter et al.
styrene under supercritical CO2 condition and as anticancer agents on various human cancer
cell lines. Despite the lack of catalytic activity, the dinuclear complexes Ru2(CO)4(μ2-η2-
O2CC3F7)2(L)2 (1) show moderate cytotoxicity in vitro. The observed cytotoxicity on Me300
melanoma cells is encouraging, and further investigation on the biological potential of
these perfluorinated sawhorse-type diruthenium tetracarbonyl complexes is in progress.
4. Experimental
4.1. General remarks
All manipulations were carried out under a nitrogen atmosphere. Organic solvents were
degassed and saturated with nitrogen prior to use. Ru3(CO)12 was prepared according to
published methods [14], while butyric acid, perfluorbutyric acid, dodecanoic acid, perfluorod-
odecanoic acid, pyridine, 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane, and triphenylphos-
phine were purchased from Sigma-Aldrich and used as received. NMR spectra were
recorded on a Bruker 400 MHz spectrometer. IR spectra were recorded as KBr pellets on a
PerkinElmer 1720x FT-IR spectrometer (4000–400 cmÀ1). Electro-spray mass spectra were
obtained in positive-ion mode with an LCQ Finnigan mass spectrometer. Elemental analyzes
were performed by the Mikroelementarisches Laboratorium, ETH Zürich (Switzerland).
Column chromatography was performed using silica gel 60 (63–200, 60 Å, Brunschwig).
4.2. Preparation of sawhorse-type diruthenium tetracarbonyl complexes
A solution of Ru3(CO)12 and three equivalents of the appropriate fluorinated fatty acids in
dry tetrahydrofuran (20 mL) was heated at 110 °C in a pressure Schlenk tube for 15 h.
Then, addition of three equivalents of the axial ligand [(L= NC5H5); (L= PTA); (L= PPh3)]
under stirring at room temperature for 2 h afforded the final products. After evaporation of
the tetrahydrofuran, the complexes were isolated from the residue by precipitation from
dichloromethane/pentane. In order to improve the purity, the crude products were subjected
to chromatography on silica gel using a dichloromethane/pentane mixture as eluent (for 1b
and 2b a dichloromethane/ethanol mixture was used), and the solid obtained was dried
under vacuum.
Ru2(CO)4(μ2-η2-O2CC3F7)2(NC5H5)2 (1a)
1
Yield: 200 mg (71%). H NMR (400 MHz, CDCl3): δ = 7.46–7.50 (m, 4 H, HC5H5N), 7.90
(tt, 2 H, 3J = 8 Hz, 4J = 2 Hz, HC5H5N), 8.62–8.64 (m, 4 H, HC5H5N). 19F{1H} NMR
(376 MHz, CDCl3) δ = À81.7 (6 F), À118.8 (4 F), À128.1 (4 F). IR (KBr, cmÀ1) ν(OCO)
1650.9 vs. ν(CO) 1967.4 vs. (νCO) 1992.7 m, (νCO) 2041.6 vs. ESI-MS (positive mode): m/
z = 935.58 [M + 2 H2O + H]+. Anal. Calcd for C22H10N2O8F14Ru2∙C5H12 (970.59) C 33.41,
H 2.28, N 2.89; Found: C 33.69, H 1.88, N 3.06%.
Ru2(CO)4(μ2-η2-O2CC3F7)2(PTA)2 (1b)
1
Yield: 97 mg (59%) H NMR (400 MHz, CDCl3): δ = 4.25 (br-m, 12 H, HPTA), 4.62 (m,
12 H, HPTA). 31P{1H} NMR (162 MHz, CDCl3) δ = À54.68 ppm. 19F{1H} NMR
(376 MHz, CDCl3) δ = À81.7 (6 F), À118.6 (4 F), À128.4 (4 F). IR (KBr, cmÀ1) ν(OCO)
1663.0 vs. ν(CO) 1967.8 vs. (νCO) 1991.6 m, (νCO) 2037.4 vs. ESI-MS (positive mode):
m/z = 1055.90 [M + H]+. Anal. Calcd for C24H24N6O8F14P2Ru2∙C2H5OH∙CH2Cl2 (1365.45)
C 27.35, H 2.72, N 7.09; Found: C 27.62, H 2.66, N 6.63%.

Sawhorse-type diruthenium
Ru2(CO)4(μ2-η2-O2CC3F7)2(PPh3)2 (1c)
1759
1
Yield: 150 mg (76%) H NMR (400 MHz, CDCl3): δ = 7.39–7.45 (m, 18 H, HPPh3), 7.48–
7.55 (m, 12 H, HPPh3). 31P{1H} NMR (162 MHz, CDCl3) δ = 15.23 ppm. 19F{1H} NMR
(376 MHz, CDCl3) δ = À82.0 (6 F), À118.6 (4 F), À128.3 (4 F). IR (KBr, cmÀ1) ν(OCO)
1658.9 vs. ν(CO) 1966.4 vs. (νCO) 1991.1 m, (νCO) 2030.9 vs. ESI-MS (positive mode): m/
z = 1183.96 [M À 3 CO + H]+. Anal. Calcd for C48H30O8F14P2Ru2 (1264.81) C 45.58, H
2.39; Found: C 45.84, H 2.56%.
Ru2(CO)4(μ2-η2-O2CC11F23)2(NC5H5)2 (2a)
1
Yield: 153 mg (67%) H NMR (400 MHz, CDCl3): δ = 7.45–7.49 (m, 4 H, HC5H5N), 7.90
(tt, 2 H, 3J = 8 Hz, 4J = 2 Hz, HC5H5N), 8.62–8.64 (m, 4 H, HC5H5N). 19F{1H} NMR
(376 MHz, CDCl3) δ = À81.8 (6 F), À117.8 (4 F), À122.5 (4 F), À122.9 (20 F), À123.8
(8 F), À127.2 (4 F). IR (KBr, cmÀ1) ν(OCO) 1667.4 vs. ν(CO) 1964.0 vs. (νCO) 1984.2 m,
(νCO) 2046.5 vs. ESI-MS (positive mode): m/z = 980.97 [M – C12F23O2 – C5H5N – CO
+ H]+. Anal. Calcd for C38H10F46N2O8Ru2 (1698.56) C 26.87, H 0.59, N 1.65; Found: C
26.58, H 0.72, N 2.04%.
Ru2(CO)4(μ2-η2-O2CC11F23)2(PTA)2 (2b)
1
Yield: 56 mg (26%) H NMR (400 MHz, CDCl3): δ = 4.25 (br-m, 12 H, HPTA), 4.62 (m,
12 H, HPTA). 31P{1H} NMR (162 MHz, CDCl3) δ = À54.70 ppm. 19F{1H} NMR
(376 MHz, CDCl3) δ = À81.8 (6 F), À117.6 (4 F), À122.6 (4 F), À122.8 (16 F), À123.0
(4 F), À123.8 (4 F), À124.0 (4 F), À127.2 (4 F). IR (KBr, cmÀ1) ν(OCO) 1662.3 vs. ν(CO)
1960.6 vs. (νCO) 1982.5 m, (νCO) 2038.0 vs. ESI-MS (positive mode): m/z = 1856.77 [M
+ H]+. Anal. Calcd for C40H24N6O8F46P2Ru2∙C2H5OH (1900.74) C 26.54, H 1.59, N 4.42;
Found: C 26.59, H 1.57, N 4.31%.
Ru2(CO)4(μ2-η2-O2CC11F23)2(PPh3)2 (2c)
1
Yield: 60 mg (54%) H NMR (400 MHz, CDCl3): δ = 7.36–7.44 (m, 18 H, HPPh3), 7.46–
7.50 (m, 12 H, HPPh3). 31P{1H} NMR (162 MHz, CDCl3) δ = 15.24 ppm. 19F{1H} NMR
(376 MHz, CDCl3) δ = À81.8 (6 F), À117.57 (4 F), À122.9 (24 F), À123.8 (8 F), À127.2
(4 F). IR (KBr, cmÀ1) ν(OCO) 1658.9 vs. ν(CO) 1966.8 vs. (νCO) 1991.3 m, (νCO) 2031.9 vs.
ESI-MS (positive mode): m/z = 1692.86 [M – PPh3 – 4 CO + H]+. Anal. Calcd for
C64H30F46O8P2Ru2 (2064.93) C 37.23, H 1.46; Found: C 37.19, H 1.55%.
Ru2(CO)4(μ2-η2-O2CC3H7)2(PPh3)2 (3)
1
3
Yield: 80 mg (52%). H NMR (400 MHz, CDCl3): δ = 0.60 (t, 6 H, J = 7 Hz, CH3), 1.10–
3
1.17 (m, 4 H, CH2), 1.92 (t, 4 H, J = 7 Hz, CH2), 7.36–7.41 (m, 18 H, HPPh3), 7.54–7.57
(m, 12 H, HPPh3). 31P{1H} NMR (162 MHz, CDCl3) δ = 14.11 ppm. IR (KBr, cmÀ1) ν(OCO)
1564.1 vs. ν(CO) 1941.1 vs. (νCO) 1975.9 m, (νCO) 2018.4 vs. ESI-MS (positive mode): m/
z = 987.04 [M – CO + H]+. Anal. Calcd for C48H44O8P2Ru2 (1012.95) C 56.91, H 4.38;
Found: C 56.41, H 4.40%.
Ru2(CO)4(μ2-η2-O2CC11H23)2(PPh3)2 (4)
Yield: 108 mg (56%). H NMR (400 MHz, CDCl3): δ = 0.89 (t, 6 H, J = 7 Hz, CH3), 1.00–
1
3
3
1.11 (m, 16 H, CH2), 1.22–1.29 (m, 20 H, CH2), 1.92 (t, 4 H, J = 7 Hz, CH2) 7.36–7.40
(m, 18 H, HPPh3), 7.54–7.55 (m, 12 H, HPPh3). 31P{1H} NMR (162 MHz, CDCl3)
δ = 14.21 ppm. IR (KBr, cmÀ1) ν(OCO) 1567.6 vs. ν(CO) 1952.4 vs. (νCO) 1981.5 m, (νCO
)
2031.1 vs. ESI-MS (positive mode): m/z = 1238.33 [M]+. Anal. Calcd for C64H76O8P2Ru2
(1237.37) C 62.12, H 6.19; Found: C 62.00, H 6.12%.

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J.P. Johnpeter et al.
4.3. Catalytic experiments
4.3.1. Safety warning. Experiments involving pressurized gasses can be hazardous and
must only be conducted with suitable equipment and following appropriate safety
conditions [15].
General procedure for hydrogenation of styrene in supercritical carbon dioxide: the reac-
tion was carried out in a 125 mL stainless steel reactor equipped with a magnetic stirrer.
The reactor was purged with argon prior to the introduction of Ru-catalyst and styrene
(amount of catalyst = 0.02 mmol, substrate/catalyst ratio = 500) via a cannula transfer. When
methanol was used as co-solvent, catalysts were prior dissolved in 1 mL of degassed
methanol. After introduction of H2 (10 bar), CO2 was admitted, leading to a total reaction
pressure of 120 bar. The reaction temperature was controlled by an internal thermocouple.
After a reaction time of 16 h, the reactor was cooled down to 0 °C, the pressure was gently
released, and the liquid phase was transferred to a Schlenk tube. Trap-to-trap distillation
under vacuum at ambient temperature allowed separation of volatile compounds that were
quantitatively analyzed by GC (Thermo Scientific FOCUS GC, TR-Wax 30 m capillary
column, FID detector).
4.4. Cell culture
Human lung (A549) and cervix (HeLa) cancer cells were obtained from the American Tissue
Type Culture Collection (Manassas, VA, USA). A2780s ovarian cancer cells were obtained
from the ECACC (Salisbury, UK). Human Me300 melanoma cells were kindly provided by
D. Rimoldi, Ludwig Institute of Cancer Research, Lausanne branch. HeLa and A549 cells
were routinely grown in Dulbecco’s modified Eagle’s medium containing 4.5 g/L glucose,
while A2780 and Me300 were grown in RPMI 1640 medium both supplemented with 10%
heat-inactivated fetal calf serum and antibiotics (all from Gibco, Basel, Switzerland).
4.5. Evaluation of the cytotoxicity of the sawhorse-type diruthenium tetracarbonyl
complexes
Cells in 96-well plates (Costar, Corning, USA) were exposed at 37 °C to increasing
concentrations of complexes in complete culture medium for 72 h (5 mM stock solution in
DMSO). After washing with phosphate-buffered saline (PBS), the supernatants were
replaced with fresh medium and cell survival was measured using the 3-(4,5-dimethyl-2-
thiazoyl)-2,5-diphenyltetrazolium bromide (MTT) test. MTT (Merck) was added at 250 μg/
mL and incubation was continued for 2 h, as previously described [16]. Then, the cell
culture supernatants were removed, the cell layer was dissolved in isopropanol/0.04 N
HCl, and the absorbance at 540 nm was measured in a 96-well multiwell-plate reader
(iEMS Reader MF, Labsystems, Bioconcept, Switzerland) and compared with the values of
control cells incubated without complexes. Experiments were conducted in triplicate wells
and repeated three times.
4.6. Single-crystal X-ray structure analyses
Crystals of 1a and 3, prepared by slow diffusion of pentane in a dichloromethane solution
of 1a and 3, were mounted on a Stoe Image Plate Diffraction system equipped with a /

Sawhorse-type diruthenium
1761
Table 3. Crystallographic and structure refinement parameters for 1a and 3.
1a
3
Chemical formula
Formula weight
Crystal system
Space group
Crystal color and shape
Crystal size
a (Å)
C22H10F14N2O8Ru2
898.46
C48H44O8P2Ru2
1012.91
Monoclinic
C 2/c (No. 15)
Yellow block
0.24 Â 0.20 Â 0.17
15.630(3)
Monoclinic
C 2/c (No. 15)
Yellow block
0.25 Â 0.23 Â 0.18
24.7037(11)
9.5100(3)
b (Å)
17.900(4)
c (Å)
10.860(2)
106.41(3)
2914.6(10)
4
18.9324(9)
102.530(4)
4341.9(3)
β (°)
V (Å3)
Z
4
T (K)
293(2)
2.048
1.175
173(2)
1.550
0.824
Dc (g cmÀ3
)
μ (mmÀ1
)
Scan range (°)
2.28 < h < 26.10
2797
1918
1.69 < h < 29.22
5854
4532
Unique reflections
Observed refls. [I > 2σ(I)]
Rint
0.0441
0.0842
Final R indices [I > 2σ(I)]⁄
R indices (all data)
Goodness-of-fit
0.0440, wR2 0.1231
0.0616, wR2 0.1304
0.998
1.053, À0.531
0.0491, wR2 0.0876
0.0734, wR2 0.0944
1.044
0.896, À0.799
Max, Min Δρ/e (ÅÀ3
)
⁄Structures were refined on Fo2: wR2 = [Σ[w(Fo À Fc2)2]/Σw(Fo2)2]1/2, where wÀ1 = [Σ(Fo2) + (aP)2 + bP] and
2
P= [max(Fo2, 0) + 2Fc2]/3.
circle goniometer using Mo-Kα graphite monochromated radiation (λ = 0.71073 Å) with /
range 0–200°. The structures were solved by direct methods using SHELXS-97, while the
refinement and all further calculations were carried out using SHELXL-97 [17]. Hydrogens
were included in calculated positions and treated as riding atoms using the SHELXL
default parameters. The non-H atoms were refined anisotropically using weighted full-
matrix least-squares on F2. In 3, the two butyryl chains were disordered, pointing away
from each other, with a 50:50 occupancy ratio. Crystallographic details are summarized in
table 3. figure 3 was drawn with ORTEP [18].
Supplementary material
CCDC-914514 1a and 914515 3 contain the supplementary crystallographic data for this
paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.
html [or from the Cambridge Crystallographic Data Center, 12 Union Road, Cambridge
CB2 1EZ, UK; Fax: (internet.)+441223/336033; Email: deposit@ccdc.cam.ac.uk].
Acknowledgements
Financial support for this work by the Swiss National Science Foundation, the Centre
National de la Recherche Scientifique (CNRS-France) and a generous loan of ruthenium
chloride hydrate from the Johnson Matthey Research Centre are gratefully acknowledged.

1762
J.P. Johnpeter et al.
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