Synthesis, structural characterization and biological activity against several human tumor cell lines of four rhenium(I) diseleno-ethers complexes: Re(CO)3Cl(PhSe(CH2)2SePh), Re(CO) 3Cl(PhSe(CH2)

Article abstract of DOI:10.1016/j.poly.2010.10.026

Four novel rhenium(I) diseleno-ethers complexes, namely Re(CO) ₃Cl(PhSe(CH₂)₂SePh) (5), Re(CO) ₃Cl(PhSe(CH₂)₃SePh) (6), Re(CO) ₃Cl(HO₂C-CH₂Se(CH₂

Full text of DOI:10.1016/j.poly.2010.10.026

Polyhedron 30 (2011) 347–353
Contents lists available at ScienceDirect
Polyhedron
journal homepage: www.elsevier.com/locate/poly
Synthesis, structural characterization and biological activity against
several human tumor cell lines of four rhenium(I) diseleno-ethers
complexes: Re(CO)3Cl(PhSe(CH2)2SePh), Re(CO)3Cl(PhSe(CH2)3SePh),
Re(CO)3Cl(HO2C–CH2Se(CH2)2SeCH2–CO2H) and
Re(CO)3Cl(HO2C–CH2Se(CH2)3SeCH2–CO2H)
a,
b
c
Anthony Kermagoret a, Georges Morgant a, , Jean d’Angelo , Alain Tomas , Pascal Roussel ,
⇑
⇑
Gérard Bastian d, Philippe Collery e, Didier Desmaële a
a Laboratoire BioCIS, UMR CNRS 8076, IFR 141, Université Paris-Sud, Faculté de Pharmacie, 5 rue J.-B. Clément, 92296 Châtenay-Malabry, France
b Laboratoire de Cristallographie et RMN biologiques, UMR CNRS 8015, Université Paris Descartes, Faculté de Pharmacie, 4 Avenue de l’Observatoire, 75005 Paris, France
c Unité de Catalyse et Chimie du Solide, UMR CNRS 8181, Ecole Nationale Supérieure de Chimie de Lille, BP 90108, 59652 Villeneuve d’Ascq, France
d Laboratoire de Pharmacologie, CHU Pitié Salpêtrière, 91 Boulevard de l’Hôpital, 75013 Paris, France
e Société de Coordination de Recherches Thérapeutiques, 30 Avenue du Port, 20200 Algajola, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 June 2010
Accepted 31 October 2010
Available online 9 November 2010
Four novel rhenium(I) diseleno-ethers complexes, namely Re(CO)3Cl(PhSe(CH2)2SePh) (5), Re(CO)3Cl(Ph-
Se(CH2)3SePh) (6), Re(CO)3Cl(HO2C–CH2Se(CH2)2SeCH2–CO2H) (7) and Re(CO)3Cl(HO2C–CH2Se(CH2)3-
SeCH2–CO2H) (8), have been synthesized by reaction of Re(CO)5Cl with the corresponding
bidentate ligands. Structures of 5 and 6 were established by single-crystal X-ray diffraction analysis.
Complexes 7 and 8 were identified by elemental analysis, 1H NMR-, IR- and mass spectroscopy. The
antiproliferative activity of these complexes against four solid human tumor cells was determined. The
water-soluble disodium salts of complexes 7 and 8 exhibited marked activities against MCF-7 breast
cancer cells.
Keywords:
Rhenium(I) complexes
Diseleno-ethers ligands
X-ray structures
Cytotoxicity
Ó 2010 Elsevier Ltd. All rights reserved.
MTT
1. Introduction
carbonyl ligands of the kinetically inert [Re(CO)3]+ core serve to fix
until three coordination sites about the metal, leaving available
Cisplatin and some platinum-based related drugs exhibit an
outstanding effectiveness in the treatment of a variety of neoplas-
tic diseases. However, the clinical success of these drugs is limited
by significant side effects, due in part to the inherent toxicity of
platinum element (particularly, its nephrotoxicity), stimulating
the search for non-platinum-metal antitumor agents [1,2]. In this
respect, since rhenium, a heavy metal member of group 7 of the
Periodic Table (atomic number 75) seems to be one of the least
toxic of the metallic elements, Re-based antitumor agents consti-
tute promising candidates for clinical development [3,4]. A conve-
nient access to such agents rests on the observation that the three
two positions for ligand substitution [4]. On this basis, numerous
Re(I)-based complexes were elaborated via displacement of two
carbonyls of the Re(I)–pentacarbonyl complex Re(CO)5Cl by biden-
date ligands bearing various donor atoms (O, S, Se, Te, N, P). As
selenium has demonstrated antioxidant and antimutagenic prop-
erties, as well as a protective effect against cancer development
[5–7], this element may play a major role in coordinating rhenium
for the elaboration of Re-based antitumor agents.
In the present study, we describe the synthesis, structural char-
acterization and biological activity against several human tumor
cells of the four title rhenium(I) diseleno-ethers complexes. The
two first complexes 5, 6 are neutral species. Since the advantage
of all ionic compounds over neutral species is their improved sol-
ubility in water, which markedly facilitates their application in bio-
logical systems, we have also synthesized the two Re-complexes 7,
8 bearing both two carboxylic acid functions, which have then
been derivatized into water-soluble disodium salts.
⇑
Corresponding authors. Tel.: +33 146835463 (G. Morgant), tel.: +33 146835699;
fax: +33 146835752 (J. d’Angelo).
E-mail address: georges.morgant@u-psud.fr (G. Morgant).
0277-5387/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.poly.2010.10.026

348
A. Kermagoret et al. / Polyhedron 30 (2011) 347–353
nate [NCSe(CH2)3SeCN] with NaOH and NaBH4, and reaction with
sodium bromoacetate, according to Scheme 1.
2. Results and discussion
2.1. Synthesis of ligands 1–4
2.2. Synthesis and structural characterization of rhenium complexes
5–8
The general method for the synthesis of the bidentate diseleno-
ethers ligands used in this work was the reduction of the Se–Se or
Se–CN bonds of the starting materials to form the nucleophilic
RSeÀ ions which reacted with different halogenoalkyls. Ligands
PhSe(CH2)2SePh (1) and PhSe(CH2)3SePh (2) were prepared
according to the literature by reduction of Ph2Se2 with sodium
hydroxymethanesulfonite in aqueous ethanol and reaction with
1,2-dibromoethane or 1,3-dibromopropane, respectively [8]. Li-
gand HOOC–CH2Se(CH2)2SeCH2–COOH (3) was prepared according
to the literature [9]. The new ligand HOOC–CH2Se(CH2)3SeCH2–
COOH (4) was synthesized by treatment of propylene diselenocya-
Numerous Re(I)-complexes have efficiently been synthesized by
reaction of commercially available Re(CO)5Cl with appropriate li-
gands at reflux in THF [10–12]. This method has already been ap-
plied to diseleno-ethers ligands [13]. The reaction of Re(CO)5Cl
with ligands 1, 2, 3 and 4 leads to the formation of complexes 5,
6, 7 and 8, respectively (for a synthesis of a sulfur analog of com-
plex 7, see Ref. [14]). Structures of complexes 5 and 6 were unam-
biguously established through single-crystal X-ray diffraction
analysis (selected bond parameters are collected in Tables 1 and
2). Structures of complexes 7 and 8 were determined through ele-
mental analysis, IR-, 1H NMR- and mass spectroscopy. In this
respect, the facial arrangement of the carbonyl groups in all com-
plexes is evidenced from the CO-stretching absorptions in the IR
1. NaOH, aq.
2. NaBH4
spectra. The three strong
m
(CO) stretching bands appear in the re-
indicating the presence of the
3. 2 equiv. BrCH 2CO2Na
4. HCl aq
gion of 2030–1860 cmÀ1
,
Se
Se
fac-[Re(CO)3]+ core [15]. Regarding the 1H NMR spectra, it should
be pointed out that the methylenes regions of most of the com-
plexes exhibit predictably complex absorptions at most tempera-
tures, due to the interconversion of stereoisomers occurring via
pyramidal inversion at the coordinated seleno-ether donors (a
slow process on the NMR time scale, the energy barrier associated
NCSe
SeCN
CO2H
CO2H
4
Scheme 1. Synthesis of ligand 4.
Table 1
Table 2
Selected bond distances (Å) and bond angles (°) for complex 5.
Selected bond distances (Å) and bond angles (°) for complex 6.
Bond lengths
Bond lengths
Re(1)–Se(1)
Re(1)–Se(2)
Re(1)–C(1)
Re(1)–C(2)
Re(1)–C(3)
Re(1)–Cl(1)
Se(1)–C(4)
Se(1)–C(10)
Se(2)–C(5)
Se(2)–C(20)
O(1)–C(1)
2.6050(4)
2.5939(3)
1.899(2)
1.922(2)
1.921(2)
2.4797(6)
1.972(2)
1.929(2)
1.957(2)
1.927(2)
1.158(3)
1.149(3)
1.153(3)
Re(1)–Se(1)
Re(1)–Se(2)
Re(1)–C(1)
Re(1)–C(2)
Re(1)–C(3)
Re(1)–Cl(1)
Se(1)–C(4)
Se(2)–C(6)
Se(1)–C(10)
Se(2)–C(20)
O(1)–C(1)
2.6277(4)
2.6298(4)
1.987(5)
1.928(4)
1.928(3)
2.4800(9)
1.977(4)
1.980(4)
1.933(3)
1.936(4)
1.048(6)
1.151(4)
1.150(4)
O(2)–C(2)
O(3)–C(3)
O(2)–C(2)
O(3)–C(3)
Bond angles
Bond angles
Se(1)–Re(1)–Se(2)
Se(1)–Re(1)–C(1)
Se(2)–Re(1)–C(1)
Se(1)–Re(1)–C(2)
Se(2)–Re(1)–C(2)
C(1)–Re(1)–C(2)
Se(1)–Re(1)–C(3)
Se(2)–Re(1)–C(3)
C(1)–Re(1)–C(3)
C(2)–Re(1)–C(3)
Se(1)–Re(1)–Cl(1)
Se(2)–Re(1)–Cl(1)
C(1)–Re(1)–Cl(1)
C(2)–Re(1)–Cl(1)
C(3)–Re(1)–Cl(1)
Re(1)–Se(1)–C(4)
Re(1)–Se(1)–C(10)
C(4)–Se(1)–C(10)
Re(1)–Se(2)–C(5)
Re(1)–Se(2)–C(20)
C(5)–Se(2)–C(20)
Re(1)–C(1)–O(1)
Re(1)–C(2)–O(2)
Re(1)–C(3)–O(3)
Se(1)–C(4)–C(5)
Se(2)–C(5)–C(4)
85.11(2)
90.42(6)
94.58(7)
174.93(7)
89.83(7)
90.31(9)
97.15(7)
174.41(6)
90.53(9)
87.87(9)
82.92(2)
80.95(2)
172.25(6)
95.98(7)
94.22(7)
99.21(7)
109.97(6)
97.92(9)
102.72(7)
105.42(6)
102.39(9)
178.16(9)
177.8(2)
176.4(2)
111.5(2)
115.4(2)
Se(1)–Re(1)–Se(2)
Se(1)–Re(1)–C(1)
Se(2)–Re(1)–C(1)
Se(1)–Re(1)–C(2)
Se(2)–Re(1)–C(2)
C(1)–Re(1)–C(2)
Se(1)–Re(1)–C(3)
Se(2)–Re(1)–C(3)
C(1)–Re(1)–C(3)
C(2)–Re(1)–C(3)
Se(1)–Re(1)–Cl(1)
Se(2)–Re(1)–Cl(1)
C(1)–Re(1)–Cl(1)
C(2)–Re(1)–Cl(1)
C(3)–Re(1)–Cl(1)
Re(1)–Se(1)–C(4)
Re(1)–Se(1)–C(10)
C(4)–Se(1)–C(10)
Re(1)–Se(2)–C(6)
Re(1)–Se(2)–C(20)
C(6)–Se(2)–C(20)
Re(1)–C(1)–O(1)
Re(1)–C(2)–O(2)
Re(1)–C(3)–O(3)
Se(1)–C(4)–C(5)
Se(2)–C(6)–C(5)
81.86(12)
87.67(11)
89.10(10)
174.09(10)
92.30(10)
91.35(15)
96.62(10)
178.17(10)
89.84(14)
89.21(14)
90.04(2)
90.44(2)
177.71(12)
90.91(11)
90.56(10)
105.58(12)
110.23(10)
96.19(16)
106.36(11)
110.53(10)
94.70(16)
176.7(4)
179.7(3)
178.0(3)
112.2(2)
114.6(3)

A. Kermagoret et al. / Polyhedron 30 (2011) 347–353
349
Cl
CO
Se
Se
Se
Se
Re
Re
Cl
5
CO
CO
OC
OC
CO
6
Cl
CO
Re
HO2C
Se
HO2C
Se
CO2H
CO2H
Se
Se
Re
CO
8
CO
CO
OC
OC
Cl
7
Fig. 1. Canonical representations of complexes 5–8.
with inversion at selenium is higher than at sulfur), and were not
analyzed in any detail [13]. Note in this respect that evidence for
these invertomers comes from the intriguing spectrum of the six-
membered ring adduct 6, where the complex resonance pattern
at the methylenes region proved unchanged in a wide temperature
range, suggesting that the chair-to-chair ring reversal is locked on
the NMR time scale (see Section 4.2.2.2 and Fig. 8). Canonical rep-
resentations of complexes 5–8 are depicted in Fig. 1.
The angles: Se(1)–Re(1)–C(2) = 174.93(7)°, Se(2)–Re(1)–C(3) =
174.41(6)° and C(1)–Re(1)–Cl(1) = 172.25(6)° result in a slightly
distorted octahedral coordination around the metal atom (Fig. 3).
Regarding the five-membered ring system, the four atoms Se(1)–
Re(1)–Se(2)–C(5) are nearly coplanar within 0.03 Å; the fifth atom
C(4) is out of this plane by 0.75 Å. The two phenyl rings attached to
the selenium atoms are syn, the two angles Re(1)–Se(1)–C(10) and
Re(1)–Se(2)–C(20) are +109.97° and +105.42°, respectively. It is
noteworthy that the chlorine atom at the rhenium center is anti
to the phenyl rings, in contrast to complex 6 (see below).
The X-ray structure of complex
5 (Fig. 2) revealed that
one bidentate diseleno-ethers chain is chelated to the Re center.
As depicted in Fig. 4, complex 6 has one bidentate diseleno-
ethers chain chelated to the Re(1) center. The angles: Se(1)–
Re(1)–C(2) = 174.09(10)°, Se(2)–Re(1)–C(3) = 178.17(10)° and
C(1)–Re(1)–Cl(1) = 177.71(12)° produce a slightly distorted octa-
hedral coordination around the metal. Due to the significant
Re–Se and C–Se distances (2.63 Å and 1.93 Å, respectively), the
six-membered ring adopts a distorted chair-like conformation
(Fig. 5), with the two phenyl rings lying on a syn, pseudo-equatorial
position at the selenium atoms, the two angles Re(1)–Se(1)–C(10)
and Re(1)–Se(2)–C(20) are +110.23° and +110.53°, respectively. It
is interesting to note that the tellurium analog of complex 6
(which, in addition to the substitution of Se atoms by Te atoms, dif-
fers from 6 by the presence at Re center of a bromine atom instead
of the chorine) adopts a boat-like conformation in the solid state
[16]. The two selenium atoms Se(1), Se(2) and the two carbon
atoms C(4), C(6) are almost coplanar within 0.02 Å; the Re atom
is out of this plane by +1.637 Å, and the C(5) atom by À0.729 Å.
The chlorine atom at rhenium center is syn to the two phenyl rings.
Fig. 2. Labeled CAMERON diagram of C17H14O3ClSe2Re (5). Ellipsoids are drawn at a
50% probability level.
2.3. Biological activity against several human tumor cell lines of
complexes 5–8
The antiproliferative activity of rhenium complexes on four
human solid tumor cells: HT 29 (colorectal cancer cells), MCF-7
(hormone-dependent breast cancer cells), A 549S (lung adenocar-
cinoma cells) and HeLa (solid uterine carcinoma cells) have been
studied in this work following the standard procedure (see Section
4.3). However, because of the high insolubility in water of com-
plexes 5 and 6, the corresponding biological experiments were
severely affected by the high concentration of DMSO required to
make soluble these drugs. The advantage of complexes 7 and 8
was the presence in both molecules of two carboxylic acid groups,
precursors of the water-soluble disodium salts, which were en-
gaged in the next biological experiments. The pattern of cytotoxic
activity of these two salts showed high activities against MCF-7
breast cancer cells, the salt of complex 8 was the most effective.
However, these salts showed almost no activity against the three
Fig. 3. Coordination octahedron around the Re center in complex 5.

350
A. Kermagoret et al. / Polyhedron 30 (2011) 347–353
Fig. 4. Labeled CAMERON diagram of C18H16O3ClSe2Re (6). Ellipsoids are drawn at a 50% probability level.
Fig. 5. Chair-like conformation of complex 6.
Table 3
IC50 of disodium salt of complex 8 against several human
tumor cell lines.
Cell lines
IC50 (lM)
Fig. 6. Cytotoxicity of disodium salts of complexes 7 and 8 against MCF-7 tumor
cell line.
HeLa
75.1
A 549S
HT 29
MCF-7
131.5
>500
4.75
was the presence in both molecules of two carboxylic acid groups,
precursors of the water-soluble disodium salts, which were en-
gaged in the cytotoxicity experiments. These salts exhibited a
marked activity against MCF-7 breast cancer cells, but an apparent
lack of activity against HT29, A549 and HeLa cell lines. Further
investigations are needed to confirm these results against human
breast and ovarian cancer cell lines and to study the effect of com-
bined treatment, including complexes 7 and 8 and various antitu-
mor agents, in order to emphasize any drug sequences interaction
[3].
other solid tumor cells (Table 3 and Fig. 6). It is noteworthy that
the remarkable cytotoxicity exhibited by complexes 7 and 8
against MCF-7 cell line has already been pointed out for several
other rhenium derivatives [4,10,17–21].
3. Conclusions and perspectives
Four novel rhenium(I) diseleno-ethers complexes (5–8) have
been synthesized in good yield and characterized by means of
physico-chemical measurements, including X-ray diffraction anal-
yses of complexes 5 and 6. The antiproliferative activity of these
complexes against four solid human tumor cells was determined.
However, because of the high insolubility in water of neutral com-
plexes 5 and 6, the corresponding biological experiments were se-
verely affected by the high concentration of DMSO required to
make soluble these drugs. The advantage of complexes 7 and 8
4. Experimental
4.1. Physical measurements
The IR spectra in the range of 3500–600 cmÀ1 were obtained on
a Bruker IFS28FT as neat films. The 1H NMR and 13C NMR spectra
were recorded at 300 and 75.5 MHz, respectively, on a Bruker

A. Kermagoret et al. / Polyhedron 30 (2011) 347–353
351
Avance spectrometer. A Perkin–Elmer 2400 II elemental analyzer
was used to perform the microanalyses. Mass spectra were re-
corded with a Bruker Daltonics micro TOF (ESI; positive or negative
modes; capillary voltage: 4.8 kV; nebulizer pressure: 0.2 bar;
desolvation temperature: 180 °C; desolvation gas flow rate:
4.5 l minÀ1).
The pH was adjusted to pH 1 by addition of a 6 M HCl solution.
The resulting white precipitate and the aqueous solution were
thoroughly extracted with CH2Cl2, and the organic layers were
washed with water and dried over MgSO4. After removal of the sol-
vents under reduced pressure, the residual white solid was washed
with cyclohexane and dried under vacuum. Yield: 0.380 g (65%);
m.p. 75 °C; IR 2860 (m), 2640 (m), 2510 (m), 1678 (s), 1425 (m),
1389 (m), 1271 (s), 1227 (m), 1178 (m), 1159 (m), 1116 (m), 935
4.2. Preparation of ligand 4, Re-complexes 5–8 and disodium salts of
complexes 7 and 8
(s), 765 (m), 747 (m), 648 (s) cmÀ1
;
1H NMR (DMSO-d6): d 2.00
3
(quint., 2H, CH2CH2CH2), 2.80 (t, JHH = 6.8 Hz, 4H, CH2CH2CH2),
3.20 [s (93%) and d (7%), 2J77SeH = 15.1 Hz, 4H, SeCH2CO2H], 12.50
(br s, 2H, CO2H); 13C NMR (DMSO-d6): d 22.5 [s (93%) and d (7%),
J77SeC = 67.0 Hz, SeCH2], 24.3 [s (93%) and d (7%), J77SeC = 61.8 Hz,
SeCH2], 29.6 (s, CH2CH2CH2), 172.7 (s, CO2H).
4.2.1. Synthesis of ligand 4
4.2.1.1. Synthesis of propylene diselenocyanate. A mixture of finely
powdered selenium (2.0 g, 25.31 mmol) and KCN (1.5 g,
23.04 mmol) in 60 ml of acetone was stirred at reflux for 2 days.
After removal of the excess of selenium by filtration, 1,3-dibromo-
propane (0.5 g, 9.91 mmol) was added and the solution stirred at
reflux for 4 h. Acetone was removed under reduced pressure, and
the residual oil was dissolved in CH2Cl2 and the solution was fil-
tered. After removal of CH2Cl2 under reduced pressure, pale yellow
crystals were obtained, which were washed with cyclohexane and
4.2.2. Synthesis of rhenium complexes 5–8
4.2.2.1. Synthesis of complex 5. To a solution of ligand 1 [PhSe(CH2)2-
SePh] (103 mg, 0.303 mmol) in 15 ml of THF was added Re(CO)5Cl
(110 mg, 0.304 mmol) and the mixture was stirred at reflux over-
night. THF was removed under reduced pressure, and the residual
white powder was washed with cyclohexane and dried under vac-
uum. Yield: 114 mg (58%); Anal. Calc. for: C17H14O3ClSe2Re: C,
31.61; H, 2.18. Found: C, 31.26; H, 2.19%. MS (positive mode): 669
([M+Na]+), 611 ([MÀCl]+), 583 ([MÀClÀCO]+), 555 ([MÀClÀ2CO]+);
IR: 2020 (s), 1923 (s), 1898 (s), 1575 (m), 1478 (m), 1436 (m), 1412
(m), 1099 (m), 1071 (m), 1021 (m), 837 (m), 745 (s), 688 (s), 667
dried under vacuum to give colorless crystals. Yield: 1.220 g (50%);
3
m.p. 49 °C; 1H NMR (CDCl3):
d
2.59 (q, JHH = 6.8 Hz, 2H,
CH2CH2CH2), 3.26 (t, JHH = 6.8 Hz, 4H, SeCH2); 13C NMR (CDCl3):
d 27.5 [s (93%) and d (7%), J77SeC = 53.8 Hz, SeCH2], 31.3 (s,
CH2CH2CH2), 100.6 (s, SeCN).
3
(m), 631 (m), 616 (m) cmÀ1 1H NMR (CDCl3): d 3.20 (m, 2H), 3.65
;
(m, 2H), 7.35–7.65 (m, 10H). Colorless crystals suitable for X-ray
analysis were obtained from methylene chloride.
4.2.1.2. Synthesis of 3,7-diselenanonanedioic acid (4). To a solution of
NaOH (0.500 g, 12.50 mmol) in 15 ml of a mixture ethanol/water
(2/1) was added propylene diselenocyanate (0.466 g, 1.85 mmol)
and the mixture was stirred for 2 h at room temperature to give
an orange solution. NaBH4 (0.500 g, 13.22 mmol) was added and
the mixture was stirred for 1 h at room temperature and an addi-
tional 1 h at 50 °C to give an orange solution and a yellow precip-
itate. Sodium 2-bromoacetate (0.596 g, 3.71 mmol) was added, and
the mixture was stirred overnight at room temperature. The white
precipitate was removed by filtration and the colorless solution
was concentrated under reduced pressure to a volume of 5 ml.
4.2.2.2. Synthesis of complex 6. To
a solution of ligand 2
[PhSe(CH2)3SePh] (91.3 mg, 0.258 mmol) in 15 ml of THF was
added Re(CO)5Cl (85 mg, 0.235 mmol) and the mixture was stirred
at reflux overnight. THF was removed under reduced pressure, and
the residual white powder was washed with cyclohexane and
dried under vacuum. Yield: 138 mg (89%); Anal. Calc. for:
C
18H16O3ClSe2Re: C, 32.76; H, 2.44. Found: C, 32.62; H, 2.45%. MS
(positive mode): 625 ([MÀCl]+, see Fig. 7); IR: 2026 (s), 1929 (s),
Fig. 7. Peak pattern of [MÀCl]+ ion in the mass spectrum of compound 6,
Fig. 8. 1H NMR spectrum of compound 6 showing the complex absorptions at the
methylenes region (1.8–4.6 ppm). In this respect, see Section 2.2.
(A) experimental spectrum and (B) simulated spectrum.

352
A. Kermagoret et al. / Polyhedron 30 (2011) 347–353
(CH2)n
CO
(CH2)n
CO
-NaCl, -Na+
Se
Se
Se
Se
O
NaO2C
Re
CO2Na
Re
CO2
CO
OC
O
CO
Cl
CO
Scheme 2. Tentative structural assignment, based on [14], for the [MÀ2NaÀCl]À ions in the mass spectra of disodium salts of complexes 7 (n = 2) and 8 (n = 3).
1906 (s), 1578 (m), 1478 (m), 1439 (m), 1219 (m), 1070 (m), 1022
(m), 999 (m), 805 (m), 737 (s), 690 (s), 669 (m), 639 (m) cmÀ1 1H
terms of cellular growth inhibition and IC50 represents the concen-
tration ( M) required to reduce the viable cell population by half).
;
l
NMR (CDCl3): d 1.8–4.6 (seven methylenes resonances, 6H, see
Fig. 8, a resonance pattern which proved almost unchanged in
the temperature range of À80 °C to +100 °C [low-temperature sol-
vent: CD2Cl2, high-temperature solvent: nitrobenzene-d5]), 7.2–8.0
(m, 10H). Colorless crystals suitable for X-ray analysis were
obtained from methylene chloride.
The method is based on the ability of living cells to reduce MTT tet-
razolium salt [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazo-
lium bromide] into MTT formazan [1-(4,5-dimethylthiazol-2-yl)-
3,5-diphenylformazan] by the mitochondrial enzyme succinate
dehydrogenase of the active living cells. At indicated time points,
culture medium was carefully aspirated, and MTT (Sigma–Aldrich)
(0.5 mg/ml) in solution into RPMI medium without Phenol Red was
added to each well. After 4 h incubation at 37 °C, the medium was
removed and the formazan crystals formed by living cells were dis-
solved in 0.1 ml of DMSO. The absorbance was measured in each
well at 570 nm with a SpectraMax 250 microplate reader (Molec-
ular Devices, USA). The 50% inhibitory concentration (IC50) was
defined as the concentration that caused a 50% of treated cell death
compared to control cells.
4.2.2.3. Synthesis of complex 7. To a solution of ligand 3 (3,6-dise-
lenaoctanedioic acid, 0.105 g, 0.35 mmol) in 15 ml of THF was
added Re(CO)5Cl (0.125 g, 0.35 mmol) and the mixture was stirred
at reflux overnight. THF was removed under reduced pressure, and
the residual white powder was washed with cyclohexane and
dried under vacuum. Yield: 0.151 g (72%); Anal. Calc. for
C9H10O7ClSe2Re: C, 17.73; H, 1.65. Found: C, 17.74; H, 1.69%. MS
(positive mode): 575 ([MÀCl]+); IR: 3170–2360 (m), 2032 (s),
1943 (m), 1914 (s), 1692 (s), 1416 (m), 1366 (m), 1309 (s), 1284
(m), 1208 (m), 1172 (m), 1140 (m), 1094 (m), 892 (m), 853 (m),
4.4. X-ray diffraction measurements
;
798 (s), 706 (m), 660 (m), 631 (m) cmÀ1 1H NMR (DMSO-d6): d
Diffraction data were collected with a Bruker-SMART three-axis
diffractometer equipped with a SMART 1000 CCD area detector
3.05 (s, 2H), 3.25 (s, 2H), 3.35 (br s, 4H).
using graphite monochromated Mo K
a X-radiation (wavelength
4.2.2.4. Synthesis of complex 8. To a solution of ligand 4 (3,7-dise-
lenanonanedioic acid, 0.135 g, 0.43 mmol) in 15 ml of THF was
added Re(CO)5Cl (0.154 g, 0.43 mmol) and the mixture was stirred
at reflux overnight. THF was removed under reduced pressure, and
the residual white powder was washed with cyclohexane and
dried under vacuum. Yield: 0.240 g (90%); Anal. Calc. for
k = 0.71073 Å) at 100 K. Data collection and processing were per-
formed using Bruker SMART programs [22] and empirical absorption
correction was applied using SADABS computer program [22]. The
structure was solved by direct methods using SIR97 [23], and re-
fined by full-matrix least-squares based on F using CRYSTALS software
[24]. The molecule was drawn using the CAMERON program [25]. All
C
10H12O7ClSe2Re: C, 19.25; H, 1.94. Found: C, 19.46; H, 1.97%. MS
(positive mode): 589 ([MÀCl]+); IR: 3330–2340 (m), 2029 (s),
1935 (s), 1895 (s), 1731 (s), 1699 (s), 1415 (m), 1351 (m), 1282
(m), 1249 (m), 1206 (s), 1186 (m), 1092 (m), 834 (m), 785 (m),
Table 4
Crystal data and structure refinement parameters for complexes 5 and 6.
Complex
5
6
752 (m), 670 (m), 637 (m), 624 (s), 605 (m) cmÀ1 1H NMR
;
Empirical formula
Molecular weight
Color
Crystal system
Space group
a (Å)
C
17H14O3ClSe2Re
C18H16O3ClSe2Re
659.90
colorless
orthorhombic
Pbca
14.522(1)
13.105(1)
20.470(1)
90
90
90
3895.4(4)
8
2.25
(CD3OD): d 2.6–3.9 (m, 10H).
645.87
colorless
monoclinic
P21/c
15.1625(10)
7.6292(10)
16.8518(10)
90
4.2.3. Synthesis of disodium salts of complexes 7 and 8
4.2.3.1. General procedure. To a solution of complex (0.55 mmol) in
20 ml of ethanol was added Na2CO3 (0.122 g, 1.15 mmol) and the
mixture was stirred overnight at room temperature. The excess
of Na2CO3 was removed by filtration and ethanol was evaporated
under reduced pressure. The residual white powder was washed
with diethyl ether and dried under vacuum. Yield: 90%. Disodium
salt of 7: Anal. Calc. for C9H8O7ClNa2Se2Re, 0.25 C2H5OH: 17.16;
H, 1.44. Found: C, 17.25; H, 1.99%. MS (negative mode): 573
([MÀ2NaÀCl]À, see Scheme 2; IR: 2031 (s), 1909 (s), 1893 (s),
1595 (s), 1374 (s), 1345 (s), 1190 (m), 1134 (m), 1089 (m), 1041),
926 (m), 870 (m), 791 (m), 625 (m), 606 (m) cmÀ1. Disodium salt
of 8: Anal. Calc. for C10H10O7ClNa2Se2Re: C, 17.99; H, 1.51. Found:
C, 17.78; H, 1.77%. MS (negative mode): 587 ([MÀ2NaÀCl]À, see
Scheme 2; IR: 2016 (s), 1909 (s), 1862 (s), 1572 (s), 1418 (m),
1374 (s), 1344 (s), 1232 (m), 1192 (m), 1092 (m), 933 (m), 874
b (Å)
c (Å)
a
(°)
b (°)
112.850(10)
90
1796.4(3)
4
2.388
1.452
c
(°)
V (Å3)
Z
Dcalc (g cmÀ3
)
Absorption coefficient (mmÀ1
F(0 0 0)
)
1.0127
2464
0.18 Â 0.25 Â 0.29
1.99–44.404
0.28/0.25/0.40
1200
Crystal size (mm3)
h Ranges (°)
0.17 Â 0.22 Â 0.27
1.457–45.225
À22.29/À15.15/
À33.33
h/k/l
T (K)
100
100
161896
5931
Nb of reflections collected
73537
Nb of reflections used P3
Parameters
r(I)
8093
218
(m), 828 (m), 731 (m), 683 (m) cmÀ1
.
226
R[F]
wR[F]
0.0200
0.0217
1.0771
0.0226
0.0232
1.0815
À1.58; 4.01
0.002367
4.3. Cytotoxicity of complexes
Goodness-of-fit on F
Residual density (e ÅÀ3
Refine ls shift/su.max
)
À1.69; 1.99
The MTT/IC50 was used to determine the chemosensitivity of
the four human cancer cell lines (cytotoxicity was estimated in
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