Cyclopentadienyltin(IV) derivatives: Synthesis, characterization and study of their cytotoxic activities

Article abstract of DOI:10.1016/j.poly.2009.05.056

The organotin compounds, [SnPh₃(C₅H₄R)] (R = Bu^t (1), CMe₂(CH₂CH₂CH{double bond, long}CH₂) (2)) and [SnPh₃(C₅Me₄R)] (R = H (3), SiMe₃ (4)), were prepared by the reaction of SnPh₃Cl with the lithium derivative of the corresponding cyclopentadiene. 1-4 have been characterized by multinuclear NMR spectroscopy (¹H, ¹³C{¹H} and ¹¹⁹Sn{¹H}). In addition, the molecular structures of 1, 2 and 4 were determined by single-crystal X-ray diffraction studies. The cytotoxic activity of the organotin(IV) complexes (1-4) was tested against human tumour cell lines 8505C anaplastic thyroid cancer, A253 head and neck tumour, A549 lung carcinoma, A2780 ovarian cancer, DLD-1 colon carcinoma. Compounds 1-4 present higher activities than cisplatin in all the studied cells. The highest sensitivity of the synthesized tin(IV) complexes was observed against A2780 ovarian cancer and DLD-1 colon carcinoma. Complex 3 presents the highest cytotoxic activity of all the studied complexes in all the cancer cells, with IC₅₀ values from 0.037 to 0.085 μM, however, its trimethylsilyl-substituted analogue (4), showed the lowest activity against all the studied cells with IC₅₀ values from 0.163 to 0.351 μM. Complexes 1 and 2 presented very similar activities on all the cancer cells (IC₅₀ values from 0.044 to 0.119 μM).

Full text of DOI:10.1016/j.poly.2009.05.056

Polyhedron 29 (2010) 16–23
Contents lists available at ScienceDirect
Polyhedron
journal homepage: www.elsevier.com/locate/poly
Cyclopentadienyltin(IV) derivatives: synthesis, characterization and study
of their cytotoxic activities
a
b
a
b
Santiago Gómez-Ruiz a, , Sanjiv Prashar , Till Walther , Mariano Fajardo , Dirk Steinborn ,
*
c
b,c,d,
*
´
Reinhard Paschke , Goran N. Kaluderovic
a Departamento de Química Inorgánica y Analítica, E.S.C.E.T., Universidad Rey Juan Carlos, 28933 Móstoles, Madrid, Spain
b Institut für Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Straße 2, D-06120 Halle, Germany
c Biozentrum, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120 Halle, Germany
d Department of Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 14, 11000 Belgrade, Serbia
a r t i c l e i n f o
a b s t r a c t
The organotin compounds, [SnPh3(C5H4R)] (R = But (1), CMe2(CH2CH2CH@CH2) (2)) and [SnPh3(C5Me4R)]
(R = H (3), SiMe3 (4)), were prepared by the reaction of SnPh3Cl with the lithium derivative of the corre-
sponding cyclopentadiene. 1–4 have been characterized by multinuclear NMR spectroscopy (1H, 13C{1H}
and 119Sn{1H}). In addition, the molecular structures of 1, 2 and 4 were determined by single-crystal X-
ray diffraction studies. The cytotoxic activity of the organotin(IV) complexes (1–4) was tested against
human tumour cell lines 8505C anaplastic thyroid cancer, A253 head and neck tumour, A549 lung carci-
noma, A2780 ovarian cancer, DLD-1 colon carcinoma. Compounds 1–4 present higher activities than cis-
platin in all the studied cells. The highest sensitivity of the synthesized tin(IV) complexes was observed
against A2780 ovarian cancer and DLD-1 colon carcinoma. Complex 3 presents the highest cytotoxic
Article history:
Available online 2 June 2009
Keywords:
Anticancer drugs
Tin
Cytotoxicity
Cyclopentadienyl ligands
Cisplatin
activity of all the studied complexes in all the cancer cells, with IC50 values from 0.037 to 0.085
ever, its trimethylsilyl-substituted analogue (4), showed the lowest activity against all the studied cells
with IC50 values from 0.163 to 0.351 M. Complexes 1 and 2 presented very similar activities on all
the cancer cells (IC50 values from 0.044 to 0.119 M).
lM, how-
l
l
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
derivatives, in order to observe the influence of the substituents at-
tached to the cyclopentadienyl ring on the final anticancer activity of
the organotin(IV) complexes. Thus, as a continuation of our work in
the synthesis of cyclopentadienyltin(IV) derivatives [40], we report
the synthesis, structural characterization and evaluation of the cyto-
toxic activity on human cancer cells of four triphenyltin(IV) com-
plexes with different cyclopentadienyl ligands (Fig. 1). One of the
studied complexes is [SnPh3{C5H4CMe2(CH2CH2CH@CH2)}], which
contains the alkenyl-substituted cyclopentadienyl ligand C5H4-
CMe2(CH2CH2CH@CH2) that has proven to induce an increase in
the cytotoxic activity of titanocene complexes [36–38], however,
in this study with cyclopentadienyltin(IV) derivatives, this positive
effect of the alkenyl substituent is not observed and, in contrast to
the results obtained for titanocene complexes [36–38], the com-
pound [SnPh3(C5Me4H)] containing a tetramethylcyclopentadienyl
moiety is the most active of the studied compounds.
Research on the synthesis and applications of metal-based
drugs are currently considered as one of the most expanding areas
in biomedical and inorganic chemistry [1–3]. Recent studies have
shown very promising in vitro antitumour properties of organotin
compounds against a wide panel of tumour cell lines of human ori-
gin [4–10]. In some cases, organotin(IV) derivatives have also
shown acceptable antiproliferative in vivo activity as new chemo-
therapy agents [11–16]. From all the studied tin(IV) derivatives,
di and triorganotin(IV) carboxylate [17–23], thiolate [24–30] and
dithiocarbamate [31] complexes have been studied extensively,
while cyclopentadienyltin(IV) derivatives have only recently been
studied very briefly [32].
In this context, and taking into account that the modification of
the cyclopentadienyl ligands has a notable effect on the antiprolifer-
ativeeffectofmetallocenecomplexesinanticancertests[33–39], we
decided to study the cytotoxic activity of cyclopentadienyltin(IV)
2. Experimental
2.1. General manipulations
* Corresponding authors. Tel.: +34 914888527; fax: +34 914888143 (S. Gómez-
´
Ruiz), fax: +38 111636061 (G.N. Kaluderovic).
All reactions were performed using standard Schlenk tube tech-
niques in an atmosphere of dry nitrogen. Solvents were distilled
E-mail addresses: santiago.gomez@urjc.es (S. Gómez-Ruiz), goran.kaluderovic@
chemie.uni-halle.de, goran@chem.bg.ac.rs (G.N. Kaluderovic
´).
0277-5387/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.poly.2009.05.056

S. Gómez-Ruiz et al. / Polyhedron 29 (2010) 16–23
17
7.56 (br m, 6H, 3J(1H–Sn) = 45.0 Hz, o-protons in SnPh3); 13C{1H}
NMR (100.6 MHz, CDCl3, 25 °C): d 28.4, 29.4 (CH2CH2), 35.2
(CMe2), 42.5 (CpC), 113.7 (CH2–CH@CH2), 90.7 (C-1 of Cp, 1J(13C–
Sn) not observed), 125.7, 153.0 (C-2 and C-3 of Cp), 128.8 (C-3
and C-5 of SnPh3, 3J(13C–Sn) = 52.5 Hz), 129.5 (C-4 of SnPh3,
4J(13C–Sn) = 12.1 Hz), 137.2 (C-2 and C-6 of SnPh3, 2J(13C–Sn) =
38.3 Hz), 138.4 (C-1 of SnPh3, 1J(13C–Sn) not observed), 140.1
(CH2–CH@CH2); 119Sn{1H} NMR (149.2 MHz, CDCl3, 25 °C):
d À101.2; MS FAB (m/e (relative intensity)): 511 (2) [M+], 433 (7)
[M+ÀHÀPh], 380 (6) [M+ÀPhÀCH2CH2CH@CH2], 351 (100)
[M+ÀC5H4(CMe2(CH2CH2CH@CH2))]. Anal. Calc. for C30H32Sn: C,
70.47; H, 6.31. Found: C, 70.10; H, 6.20%.
Fig. 1. Cyclopentadienyl derivatives used in this study.
from the appropriate drying agents and degassed before use.
SnPh3Cl and Li(C5H4But) were purchased from Aldrich and used
without further purification. Li{C5H4CMe2(CH2CH2CH@CH2)} [41],
Li(C5Me4H) [42] and Li(C5Me4SiMe3) [43] were prepared as previ-
ously reported. 1H, 13C{1H} and 119Sn{1H} NMR spectra were re-
corded on a Varian Mercury FT-400 spectrometer and referenced
to the residual deuterated solvent or to SnMe4 in the case of
119Sn{1H} NMR. Microanalyses were carried out with a Perkin–El-
mer 2400 microanalyzer. IR spectra (KBr pellets were prepared in
a nitrogen-filled glove box) were recorded on a Nicolet Avatar
380 FTIR spectrometer in the range 350–4000 cmÀ1. FAB-MS spec-
tra were recorded on a MASPEC II spectrometer with 3-nitroben-
zylalcohol as matrix.
2.4. Synthesis of [SnPh3(C5Me4H)] (3)
The preparation of 3 was carried out in an identical manner to 1.
Li(C5Me4H) (0.75 g, 5.85 mmol) and SnPh3Cl (2.25 g, 5.85 mmol).
Yield: 1.82 g, 67%. FT-IR (KBr): 3135 (m), 3063 (s), 3016 (s), 2960
(s), 2910 (s), 2854 (s), 2730 (w), 1952 (m), 1877 (m), 1817 (m),
1773 (w), 1619 (m), 1578 (m), 1480 (s), 1428 (s), 1384 (m), 1332
(m), 1258 (w), 1225 (w), 1109 (s), 1040 (m), 1022 (m), 997 (m),
908 (m), 727 (m), 670 (m), 658 (m), 555 (m), 453 (s); 1H NMR
(400 MHz, CDCl3, 25 °C):
d
1.75 (s, 6H, 4J(1H–Sn) = 19.2 Hz,
2.2. Synthesis of [SnPh3(C5H4But)] (1)
C5Me4), 1.82 (s, 6H, C5Me4), 4.09 (s, 1H, 1J(1H–Sn) = 100.1 Hz,
C5Me4H), 7.39 (br m, 9H, m- and p-protons in SnPh3), 7.50 (br m,
6H, 3J(1H–Sn) = 51.5 Hz, o-protons in SnPh3); 13C{1H} NMR
(100.6 MHz, CDCl3, 25 °C): d 11.8 (C5Me4, 3J(13C–Sn) = 9.0 Hz),
14.0 (C5Me4), 57.7 (C-1 of Cp, 1J(13C–Sn) not observed), 128.3 (C-3
and C-5 of SnPh3, 3J(13C–Sn) = 50.4 Hz), 128.9 (C-4 of SnPh3,
4J(13C–Sn) = 11.6 Hz), 130.3, 134.2 (C-2 and C-3 of Cp), 137.0 (C-2
and C-6 of SnPh3, 2J(13C–Sn) = 38.7 Hz), 138.7 (C-1 of SnPh3,
1J(13C–Sn) not observed); 119Sn{1H} NMR (149.2 MHz, CDCl3,
25 °C): d À113.8; MS FAB (m/e (relative intensity)): 472 (6)
[M++H], 395 (9) [M+ÀPh], 351 (100) [M+ÀC5Me4H], 241 (22)
[M+À3 Â Ph]. Anal. Calc. for C27H28Sn: C, 68.82; H, 5.99. Found: C,
68.69; H, 5.90%.
Li(C5H4But) (0.75 g, 5.85 mmol) was added to a solution of
SnPh3Cl (2.25 g, 5.85 mmol) in THF (50 ml) at À78 °C. The reaction
mixture was allowed to reach room temperature and stirred for
16 h. Solvent was removed by applying reduced pressure and hex-
ane (40 ml) added. The suspension was filtered and the filtrate con-
centrated (5 ml). Cooling to À30 °C yielded the title compound as a
yellow crystalline solid. Yield: 2.34 g, 85%. FT-IR (KBr): 3139 (m),
3065 (s), 2972 (s), 2912 (s), 2845 (s), 2723 (w), 1946 (m), 1887
(m), 1813 (m), 1615 (w), 1476 (s), 1432 (s), 1372 (m), 1301 (m),
1263 (w), 1190 (w), 1074 (s), 1022 (s), 997 (m), 975 (m), 890 (s),
850 (m), 829 (m), 805 (m), 725 (s), 697 (s), 669 (s), 658 (s), 643
(m), 447 (s); 1H NMR (400 MHz, CDCl3, 25 °C): d 1.03 (s, 9H, But),
5.65 (m, 2H, 3J(1H–Sn) = 61.2 Hz, C5H4), 6.57 (m, 2H, C5H4) 7.42
(br m, 9H, m- and p-protons in SnPh3), 7.56 (br m, 6H, 3J(1H–
Sn) = 50.2 Hz, o-protons in SnPh3); 13C{1H} NMR (100.6 MHz,
CDCl3, 25 °C): d 30.8 (Me of But, 3J(13C–Sn) = 9.2 Hz), 32.2 (C-ipso
of But 2J(13C–Sn) not observed), 90.7 (C-1 of Cp, 1J(13C–Sn) not ob-
served) 125.0, 154.5 (C-2 and C-3 of Cp), 128.7 (C-3 and C-5 of
SnPh3, 3J(13C–Sn) = 52.3 Hz), 129.5 (C-4 of SnPh3, 4J(13C–
Sn) = 9.2 Hz), 137.2 (C-2 and C-6 of SnPh3, 2J(13C–Sn) = 38.4 Hz),
138.4 (C-1 of SnPh3 1J(13C–Sn) not observed); 119Sn{1H} NMR
(149.2 MHz, CDCl3, 25 °C): d À101.7; MS FAB (m/e (relative inten-
sity)): 472 (1) [M++H], 395 (10) [M+ÀPh], 351 (100) [M+ÀC5H4But],
241 (13) [M+À3 Â Ph]. Anal. Calc. for C27H28Sn: C, 68.82; H, 5.99.
Found: C, 68.77; H, 5.81%.
2.5. Synthesis of [SnPh3(C5Me4SiMe3)] (4)
The preparation of 4 was carried out in an identical manner to
1. Li(C5Me4SiMe3) (0.75 g, 3.74 mmol) and SnPh3Cl (1.44 g,
3.74 mmol). Yield: 1.56 g, 77%. FT-IR (KBr): 3133 (m), 3065 (s),
3020 (s), 2960 (s), 2920 (s), 2870 (s), 2725 (w), 1949 (m), 1877
(m), 1814 (m), 1772 (w), 1623 (m), 1603 (s), 1578 (m), 1481
(s), 1429 (s), 1376 (m), 1302 (s), 1247 (m), 1205 (m), 1155 (m),
1109 (w), 1073 (m), 1022 (m), 997 (m), 960 (s), 891 (w), 836
(m), 727 (s), 698 (s), 656 (m), 628 (m), 556 (m), 452 (s); 1H
NMR (400 MHz, CDCl3, 25 °C): d À0.04 (s, 9H, SiMe3), 1.86 (s,
6H, 4J(1H–Sn) = 17.4 Hz, C5Me4), 1.90 (s, 6H, C5Me4), 7.37 (br m,
9H, m- and p-protons in SnPh3), 7.51 (br m, 6H, 3J(1H–
Sn) = 49.5 Hz, o-protons in SnPh3); 13C{1H} NMR (100.6 MHz,
CDCl3, 25 °C): d À0.2 (SiMe3), 11.4 (C5Me4, 3J(13C–Sn) not ob-
served), 15.6 (C5Me4), 61.2 (C-1 of Cp, 1J(13C–Sn) not observed),
128.1 (C-3 and C-5 of SnPh3, 1J(13C–Sn) = 48.9 Hz), 128.7 (C-4 of
SnPh3, 4J(13C–Sn) = 10.6 Hz), 129.0, 136.2 (C-2 and C-3 of Cp),
137.4 (C-2 and C-6 in SnPh3, 2J(13C–Sn) = 35.8 Hz), 139.9 (C-1 of
SnPh3 1J(13C–Sn) not observed); 119Sn{1H} NMR (149.2 MHz,
CDCl3, 25 °C): d À135.2; MS FAB (m/e (relative intensity)): 544
(5) [M+], 467 (8) [M+ÀPh], 351 (100) [M+ÀC5Me4SiMe3], 313 (9)
[M+À3 Â Ph]. Anal. Calc. for C30H36SiSn: C, 66.31; H, 6.68. Found:
C, 65.97; H, 6.52%.
2.3. Synthesis of [SnPh3{C5H4CMe2(CH2CH2CH=CH2)}] (2)
The preparation of 2 was carried out in an identical manner to 1.
Li{C5H4CMe2(CH2CH2CH@CH2)} (0.75 g, 4.46 mmol) and SnPh3Cl
(1.72 g, 4.46 mmol). Yield: 1.64 g, 72%. FT-IR (KBr): 3138 (m),
3065 (s), 3049 (s), 3018 (s), 2922 (s), 1946 (m), 1887 (m), 1871
(m), 1813 (m), 1756 (w), 1640 (s), 1579 (s), 1480 (s), 1430 (s),
1377 (m), 1300 (s), 1260 (m), 1190 (m), 1156 (m), 1075 (s), 1022
(m), 997 (m), 977 (m), 906 (m), 806 (s), 725 (s), 698 (m), 675
(m), 658 (m), 644 (w), 567 (m), 525 (m), 447 (s); 1H NMR
(400 MHz, CDCl3, 25 °C): d 1.00 (s, 6H, CMe2), 1.45, 1.78 (m, 2H
each, CH2CH2), 4.89 (cis), 4.95 (trans) (dd, 1H each,
3J(1H–1H)cis = 11.7 Hz, 3J(1H–1H)trans = 16.9 Hz, CH2–CH=CH2), 5.64
(m, 2H, 3J(1H–Sn) = 53.1 Hz, C5H4), 5.73 (m, 1H, CH2–CH=CH2),
6.55 (m, 2H, C5H4) 7.42 (br m, 9H, m- and p-protons in SnPh3),
2.6. Data collection and structural refinement of 1, 2 and 4
The data of 1, 2 and 4 were collected with a CCD Oxford Xcalibur
S (k(Mo Ka) = 0.71073 Å) using x and u scans mode. Semi-empir-

18
S. Gómez-Ruiz et al. / Polyhedron 29 (2010) 16–23
ical from equivalents absorption corrections were carried out with
SCALE3 ABSPACK [44]. All the structures were solved by direct methods
[45]. Structure refinement was carried out with SHELXL-97 [46]. All
non-hydrogen atoms were refined anisotropically, and hydrogen
atoms were calculated with the riding model and refined isotropi-
cally. Crystallographic details are listed in Table 1.
achieved in treated wells were 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30
and 100 mol/l. Each concentration was tested in triple quadru-
l
plicate on each cell line. The final concentrations (<0.1%) of DMSO
and DMF, were non-toxic to the cells. The percentages of surviv-
ing cells relative to untreated controls were determined 96 h after
the beginning of drug exposure. After 96 h treatment, the super-
natant medium from the 96-well plates was thrown away and
the cells were fixed with 10% TCA. For a thorough fixation, plates
were now allowed to stand at 4 °C. After fixation the cells were
washed in a strip washer. The washing was carried out four times
with water using alternate dispensing and aspiration procedures.
2.7. In vitro studies
2.7.1. Preparation of drug solutions
Stock solutions of the studied tin compounds were prepared in
dimethyl sulfoxide (1 and 2; DMSO, Sigma Aldrich) and dimethyl
formamide (3 and 4; DMF, Sigma Aldrich) at a concentration of
The plates were then dyed with 100 ll of 0.4% SRB for about
45 min. After dyeing the plates were again washed to remove
the dye with 1% acetic acid and allowed to air dry overnight.
100 ll of 10 mM Tris base solutions was added to each well of
the plate and absorbance was measured at 570 nm using a 96-
well plate reader (Tecan Spectra, Crailsheim, Germany). The IC50
values, defined as the concentrations of the compound at which
50% cell inhibition was observed, was estimated from the dose–
response curves.
20 mM, filtered through Millipore filter, 0.22 lm, before use, and
diluted by nutrient medium to various working concentrations.
Nutrient medium was RPMI-1640 (PAA Laboratories) supple-
mented with 10% fetal bovine serum (Biochrom AG) and penicil-
lin/streptomycin (PAA Laboratories).
2.7.2. Cell lines and culture conditions
The cell lines 8505C, A253, A549, A2780 and DLD-1 that were
included in this study, were kindly provided by Dr. Thomas Muel-
ler, Department of Hematology/Oncology, Martin Luther University
of Halle-Wittenberg, Halle (Saale), Germany. Cultures were main-
tained as monolayer in RPMI 1640 (PAA Laboratories, Pasching,
Germany) supplemented with 10% heat inactivated fetal bovine
serum (Biochrom AG, Berlin, Germany) and penicillin/streptomy-
cin (PAA Laboratories) at 37 °C in a humidified atmosphere of 5%
3. Results and discussion
3.1. Synthesis and characterization of the cyclopentadienyltin(IV)
complexes 1–4
The preparation of tin complexes was achieved via the reaction
of one equivalent of the lithium cyclopentadienyl derivative with
SnPh3Cl (Schemes 1 and 2).
(v/v) CO2.
Complexes 1–4 have been characterized by 1H, 13C{1H} and
119Sn{1H} NMR spectroscopy, mass spectrometry and elemental
analysis (see Sections 2.2–2.5). NMR spectral data for 1–4 indicated
that, in solution, only one of the possible double bond positional
isomers was present. This phenomenon differs from the observa-
tion of multiple isomers in analogous silicon and germanium
bridged cyclopentadiene ligands [48–52].
2.7.3. Cytotoxicity assay
The cytotoxic activities of the tin complexes were evaluated
using the sulforhodamine-B (SRB, Sigma Aldrich) microculture
colorimetric assay [47]. In short, exponentially growing cells were
seeded into 96-well plates on day zero at the appropriate cell
densities to prevent confluence of the cells during the period of
the experiment. After 24 h, the cells were treated with serial dilu-
tions of the studied compounds for 96 h. Final concentrations
In the 1H NMR spectra of 1–4, two different multiplets, at ca. 7.2
corresponding to the m- and p-protons and at 7.5 ppm assigned to
Table 1
Crystallographic data for 1, 2 and 4.
1
2
4
Formula
Fw
C27H28Sn
471.18
C30H32Sn
511.25
C30H36SiSn
543.37
T (K)
130(2)
130(2)
130(2)
Crystal system
Space group
a (Å)
b (Å)
c (Å)
triclinic
P1
11.0569(7)
13.7460(8)
16.5966(9)
80.945(5)
triclinic
P1
9.394(1)
11.682(1)
12.396(2)
71.007(9)
triclinic
P1
8.4654(5)
9.8404(8)
17.866(1)
93.486(6)
ꢀ
ꢀ
ꢀ
a
(°)
b (°)
88.554(5)
66.918(6)
2.2898(3)
4
1.367
1.125
86.457(9)
78.040(8)
1.2584(3)
2
1.349
1.029
101.221(6)
111.870(7)
1.3402(2)
c
(°)
V (nm3)
Z
2
Dc (Mg mÀ3
)
1.346
1.013
l
(mmÀ1
)
F(0 0 0)
960
524
560
Crystal dimension (mm)
h Range (°)
hkl Ranges
0.3 Â 0.15 Â 0.04
2.75–25.68
À12 6 h 6 12
À16 6 k 6 16
À20 6 l 6 17
8645/511/0
0.940
0.3 Â 0.1 Â 0.1
2.61–26.37
À11 6 h 6 11
À14 6 k 6 14
À15 6 l 6 15
5152/282/0
0.916
0.4 Â 0.2 Â 0.04
2.65–30.51
À12 6 h 6 11
À14 6 k 6 13
À25 6 l 6 17
8165/296/0
0.885
Data/parameters/restraints
Goodness-of-fit (GOF) on F2
Final R indices [I > 2
R indices (all data)
r
(I)]
R1 = 0.0530, wR2 = 0.1045
R1 = 0.1130, wR2 = 0.1114
1.545 and À0.542
R1 = 0.0344, wR2 = 0.0562
R1 = 0.0538, wR2 = 0.0588
1.196 and À0.583
R1 = 0.0324, wR2 = 0.0544
R1 = 0.0456, wR2 = 0.0558
0.885 and À0.353
Largest difference in peak and hole
(e ÅÀ3
)

S. Gómez-Ruiz et al. / Polyhedron 29 (2010) 16–23
19
to the low intensity of these signals, even when recording the spec-
tra at very long relaxation times. Two signals assigned to the
remaining carbon atoms of the cyclopentadienyl ring, were ob-
served at ca. 125 and 154 ppm for 1 and 2, and at ca. 130 and
135 ppm for 3 and 4.
The expected signals corresponding to the different substitu-
ents of the cyclopentadienyl moiety were observed in the 13C{1H}
NMR spectra of 1–4 (see Sections 2.2–2.5). One signal was ob-
served in the 119Sn{1H} NMR spectra of 1–4 between À100 and
À135 ppm.
Scheme 1. Synthesis of complexes 1 and 2.
The 119Sn{1H} NMR characterization of all complexes was re-
peated with the solutions being prepared in an air atmosphere.
Spectra were recorded in DMSO/CDCl3 or DMF/CDCl3 at 2, 4, 12,
24 and 48 h and no evidence of decomposition or evolution to
other tin-containing products was observed.
Complexes 1–4 were also characterized by FAB-MS. The mass
spectra showed the molecular ion peaks. Fragments indicative of
the loss of different numbers of substituents were also observed
(see Sections 2.2–2.5).
Scheme 2. Synthesis of complexes 3 and 4.
3.2. Structural studies
the o-protons of SnPh3 moiety respectively, were observed. In addi-
tion, satellite signals of the o-protons, due to coupling with the
117Sn and 119Sn isotopes at a three bond distance were observed,
however, we were unable to resolve the independent satellite sig-
nals corresponding to the two tin nuclei. Therefore, the observed
coupling constant for these protons of approximately 50 Hz is an
approximate value that can be applied to either nucleus.
The molecular structures of 1, 2 and 4 were established by sin-
gle-crystal X-ray diffraction studies. The molecular structures and
atomic numbering schemes are shown in Figs. 2–4, respectively.
Selected bond lengths and angles for 1, 2 and 4 are given in Table
2.
For 1, two almost identical crystallographic independent mole-
cules were located in the asymmetric unit, of which only one will
be discussed.
In the 1H NMR spectra of 1 and 2, two multiplets, at ca. 5.6 and
6.6 ppm, were assigned to the four C5 ring protons. This indicates
that the symmetry of the molecule is such that the alkyl substitu-
ent is located in the C-1 position of the cyclopentadienyl ring. For
the equivalent cyclopentadienyl ring protons, C-2 and C-5, at three
bond distance to the tin atom, tin satellite signals were observed
with values of 3J(1H–Sn) of ca. 30 Hz.
The molecular structures of 1, 2 and 4 are of a similar nature, all
ꢀ
of them crystallize in the triclinic space group P1 with four (1) or
two (2 and 4) molecules located in the unit cell. In the molecular
structures of 1, 2 and 4 the geometry around the tin atom is clearly
tetrahedral. The cyclopentadienyl units are essentially planar with
the C-1 atom located only 0.108 Å for 1, 0.077 Å for 2 and 0.011 Å
for 4, out of the plane defined by the other four carbon atoms (C(2)
to C(5)). Three long bond lengths of about 1.47 Å and two short
bond distances of ca. 1.35 Å are observed between the carbon
atoms of the C5 ring.
For 1, a singlet signal at 1.03 ppm was observed in the 1H NMR
spectrum and assigned to the protons of the tert-butyl group. For 2
a singlet due to the two methyl groups substituting the carbon
atom adjacent to the cyclopentadienyl ring was observed at
1.00 ppm. The alkenyl fragment exhibited five sets of signals, two
corresponding to the methylene protons (two multiplets at ca.
The hybridization of the C-1 atom of the cyclopentadienyl
moiety is sp3 and the
r-bond lengths with the tin atom of about
1.5 and 1.8 ppm), one for the proton of the C-
5.6 ppm) and two for the terminal olefinic protons (multiplets at
4.89 and 4.95 ppm).
c
(a multiplet at ca.
2.19 Å are slightly longer than those recorded for the tin-phenyl
carbon distances (ca. 2.13 Å). The tin–C-1-ring plane angles
(110.90° for 1, 111.70° for 2 and 115.86° for 4) rule out an
The 1H NMR spectra of 3 and 4 are very similar. Both spectra
show two singlets for the methyl substituents of the cyclopentadi-
enyl rings between 1.7 and 1.9 ppm, one of which corresponds to
the protons of the methyl groups in the C-2 and C-5 of the ring
and shows satellites with 4J(1H–Sn) of ca. 18 Hz, and the other to
the protons of the C-3 and C-4 methyl groups in the cyclopentadi-
enyl ligand. In the 1H NMR spectrum of 3 a signal, at 4.09 ppm,
with tin satellites (2J 1H–Sn 100.1 Hz) was recorded for the proton
in the C-1 position, while in the 1H NMR spectrum of 4 a singlet
was observed at À0.04 ppm and assigned to the trimethylsilyl
protons.
In the 13C{1H} NMR spectra of 1–4, four signals at ca. 128, 129,
137 and 139 ppm were observed for the C-3/C-5, C-4, C-1 and C-2/
C-6 carbon atoms of the phenyl groups. Tin–carbon coupling con-
stants for these signals gave values of approximately 2J(13C–Sn)
35 Hz, 3J(13C–Sn) 50 Hz, and 4J(13C–Sn) 10 Hz.
In addition to the signals assigned to the phenyl groups, three
signals were recorded for the cyclopentadienyl carbon atoms. The
C-1 atom gave a signal at ca. 100 ppm for 1 and 2 and 60 ppm
for 3 and 4. In all cases, the coupling constant at one bond distance,
between the 13C and 117Sn and 119Sn nuclei was not observed due
Fig. 2. Molecular structure and atom-labelling scheme for one of the two symmetry
independent molecules of 1 with thermal ellipsoids at 50% probability (hydrogen
atoms are omitted for clarity).

20
S. Gómez-Ruiz et al. / Polyhedron 29 (2010) 16–23
Table 2
Selected bond lengths (Å) and angles (°) for 1, 2 and 4.
1a
2
4
Sn(1)–C(1)
Sn(1)–C(11)
Sn(1)–C(21)
Sn(1)–C(31)
Sn(1)–C(41)
Si(1)–C(1)
C(1)–C(2)
C(1)–C(5)
C(2)–C(3)
C(3)–C(4)
C(4)–C(5)
C(3)–C(6)
C(6)–C(7)
C(7)–C(8)
C(8)–C(9)
C(9)–C(10)
2.183(7)/2.193(6)
2.127(7)/2.132(7)
2.147(7)/2.126(8)
2.135(7)/2.135(7)
2.197(3)
2.137(3)
2.128(3)
2.140(3)
2.189(2)
2.147(2)
2.143(2)
2.149(2)
1.907(2)
1.501(3)
1.495(3)
1.354(3)
1.444(3)
1.354(3)
1.454(9)/1.476(9)
1.459(9)/1.440(9)
1.363(9)/1.344(9)
1.435(9)/1.452(9)
1.352(9)/1.36(1)
1.49(2)/1.50(1)
1.466(4)
1.470(4)
1.346(4)
1.442(4)
1.344(4)
1.522(4)
1.541(4)
1.530(4)
1.496(5)
1.296(5)
1.54(1)/1.50(2)
C(1)–Sn(1)–C(11)
C(1)–Sn(1)–C(21)
C(1)–Sn(1)–C(31)
C(1)–Sn(1)–C(41)
C(11)–Sn(1)–C(21)
C(11)–Sn(1)–C(31)
C(21)–Sn(1)–C(31)
C(21)–Sn(1)–C(41)
C(31)–Sn(1)–C(41)
C(1)–C(2)–C(3)
C(1)–C(5)–C(4)
C(2)–C(3)–C(4)
C(3)–C(4)–C(5)
C(5)–C(1)–C(2)
C(7)–C(8)–C(9)
C(8)–C(9)–C(10)
109.4(3)/105.9(3)
113.2(3)/111.2(3)
106.8(3)/111.1(3)
105.7(1)
112.2(2)
105.9(2)
117.34(7)
110.10(7)
109.79(7)
Fig. 3. Molecular structure and atom-labelling scheme for 2 with thermal ellipsoids
at 50% probability (hydrogen atoms are omitted for clarity).
105.9(3)/109.8(3)
108.4(3)/112.4(3)
113.0(3)/106.5(3)
111.2(1)
111.1(2)
110.5(1)
105.76(8)
105.97(7)
107.37(7)
109.3(2)
109.2(2)
109.1(2)
109.6(2)
102.8(2)
109.9(6)/110.1(6)
109.0(7)/109.5(7)
107.5(6)/107.3(7)
109.3(6)/109.0(7)
103.7(6)/103.8(6)
109.7(3)
108.0(3)
107.7(3)
110.3(3)
104.2(2)
113.3(3)
126.2(3)
a
Values of the two symmetry independent molecules are given.
Selected structural data of 1, 2 and 4 can be compared with similar
cyclopentadienyltin(IV) compounds using Table 3.
3.3. Cytotoxic studies
The in vitro cytotoxicities of complexes 1–4 and cisplatin
against human tumour cell lines 8505C anaplastic thyroid cancer,
A253 head and neck tumour, A549 lung carcinoma, A2780 ovarian
cancer and DLD-1 colon carcinoma were determined by using the
sulforhodamine-B microculture colorimetric assay [47]. This study
has been carried out in order to understand the relationship be-
tween the different tin(IV) compounds and the cytotoxic activity.
The IC50 values of the studied compounds and cisplatin are sum-
marized in Table 4.
Fig. 4. Molecular structure and atom-labelling scheme for 4 with thermal ellipsoids
at 50% probability (hydrogen atoms are omitted for clarity).
Triphenyltin(IV) complexes (1–4) showed a dose-dependent
antiproliferative effect toward all cancer cell lines (Fig. 5), present-
ing, in all cases, lower IC50 values than those of cisplatin. These re-
sults indicate their high activity against the tumoural cell lines
evaluated.
p-
g1 type interaction of the metal with the aromatic ring as has
been previously observed in beryllium and zinc metallocene com-
plexes [53–59].
In contrast to the observed spectroscopic data of the complexes
1 and 2 in solution, in which the obtained signals showed that the
substituent at the cyclopentadienyl ligand was located in the C-1
position, due the rapid sigmatropic migration in solution of the
tin atom around the cyclopentadienyl ring [60], in solid state, this
substituent is located in the C-3 position, probably in order to min-
imize steric impediments as has been previously observed for
other cyclopentadienyltin(IV) derivatives [60]. Thus, complex 1
presents the But substituent at the C-3 position and shows typical
C–C bond lengths and angles. The alkenyl substituent of 2, is also
located at the C-3 atom of the C5 ring. The distance C(9)–C(10) is
typical for terminal C–C double bonds [41,61–63] and the angle
C(8)–C(9)–C(10), 126.2(3)° confirms the sp2 hybridization of C(9).
In contrast to the results obtained for titanocene complexes
with similar cyclopentadienyl ligands [36–38], 3 (which contains
the tetramethylcyclopentadienyl moiety) is the most active com-
pound with cytotoxic activities from 17 (against A253) to 104
times (against DLD-1) better than that of cisplatin, and IC50 values
between ca. 0.037 and 0.085 lM. Complexes 1 and 2, which con-
tain alkyl and alkenyl-substituted cyclopentadienyl ligands, pres-
ent comparable cytotoxic activities on all the studied cells,
showing IC50 values from 0.044 to 0.119 lM. However, their activ-
ities are, in all cases, lower than those observed for 3, indicating the
absence of the positive effect on the cytotoxic activity provided by
alkenyl-substituted cyclopentadienyl ligands [36–38], in tin(IV)
complexes.

S. Gómez-Ruiz et al. / Polyhedron 29 (2010) 16–23
21
Table 3
Selected structural data of cyclopentadienyltin(IV) compounds.
Compound
Sn–C1(Cp) (Å)
C–C(Cp) (Å)
C@C(Cp) (Å)
Si–C1(Cp) (Å)
Reference
This work
[SnPh3(C5H4But)] (1)a
2.183(7)
2.193(6)
1.435(9)
1.440(9)
1.452(9)
1.454(9)
1.459(9)
1.476(9)
1.442(4)
1.466(4)
1.470(4)
1.444(3)
1.495(3)
1.501(3)
1.457(6)
1.459(5)
1.475(6)
1.480(5)
1.480(6)
1.497(5)
1.456(3)
1.502(3)
1.505(3)
1.363(9)
1.344(9)
1.352(9)
1.36(1)
[SnPh3{C5H4CMe2(CH2CH2CH@CH2)}] (2)
[SnPh3(C5Me4SiMe3)] (3)
2.197(3)
2.189(2)
1.344(4)
1.346(4)
This work
This work
[40]
1.354(3)
1.354(3)
1.907(2)
[SnMe2(C5Me4H)2]a
2.195(4)
2.205(4)
2.206(4)
2.202(4)
1.353(6)
1.353(6)
1.356(5)
1.359(5)
[SnMe2(C5Me4SiMe3)2]
2.190(2)
1.350(3)
1.358(3)
1.905(2)
[40]
a
Values for the two independent molecules found in the asymmetric unit are given.
Table 4
IC50 M) for the 96 h of action of the studied compounds and cisplatin on 8505C anaplastic thyroid cancer, A253 head and neck tumour, A549 lung carcinoma, A2780 ovarian
cancer and DLD-1 colon carcinoma determined by sulforhodamine-B microculture colorimetric assay.
(l
Compound
IC50 SD
8505C
A253
A549
A2780
DLD-1
1
2
3
4
0.103 0.015
0.110 0.011
0.085 0.007
0.343 0.046
5
0.077 0.012
0.118 0.028
0.045 0.004
0.351 0.045
0.8
0.079 0.002
0.108 0.018
0.038 0.003
0.384 0.021
1.5
0.042 0.004
0.061 0.002
0.037 0.007
0.163 0.002
0.55
0.044 0.007
0.119 0.004
0.048 0.002
0.309 0.003
5
Cisplatin
Fig. 5. Representative graphs showing survival of 8505C, A253, A549, A2780 and DLD-1 cells grown for 96 h in the presence of increasing concentrations of the studied
compounds (1–4). Standard deviations are omitted for clarity.
Interestingly, the trimethylsilyl-substituted complex 4 showed
lower in vitro antitumoural activity in comparison to other studied
derivatives, with IC50 values from ca. 0.163 to 0.351
enhancement of the antiproliferative activity of SiMe3 groups
lM. Again, the

22
S. Gómez-Ruiz et al. / Polyhedron 29 (2010) 16–23
[7] M. Gielen, M. Biesemans, D. De Vos, R. Willem, J. Inorg. Biochem. 79 (2000)
139.
reported by McGowan and coworkers using trimethylsilyl-substi-
tuted titanocene complexes [64], is not observed for tin(IV) com-
plexes. In addition, complexes 1–4 present substantially higher
cytotoxic activity on cancer cell lines (up to 5000 times) than other
reported cyclopentadienyltin(IV) derivatives [32].
With these data, one can conclude a ligand-dependent activity
of the studied complexes on the different cells. Complexes bearing
monosubstituted cyclopentadienyl ligands present different cyto-
toxic activities with respect to their tetra- and pentasubstituted
analogues. In addition, one can conclude a different behaviour in
the influence of the substituents of the cyclopentadienyl ligands
on the final cytotoxic activity of titanocene and organotin(IV) com-
plexes, indicating a substantial difference in the anticancer mech-
anism of these two class of metal-based drugs.
[8] M. Gielen, Appl. Organomet. Chem. 16 (2002) 481.
[9] S.K. Hadjikakou, N. Hadjiliadis, Coord. Chem. Rev. 253 (2009) 235.
[10] M. Gielen, A.G. Davies, K. Pannell, E. Tiekink, Tin Chemistry: Fundamentals,
Frontiers, and Applications, John Wiley and Sons, Wiltshire, 2008.
[11] L. Nagy, A. Szorcsik, K. Kovacs, Pharm. Hungarica 70 (2000) 53.
[12] M. Nath, S. Pokharia, R. Yadav, Coord. Chem. Rev. 215 (2001) 99.
[13] M. Gielen, in: NATO ASI Ser. 2, vol. 26, 1997, p. 445.
[14] D. De Vos, R. Willem, M. Gielen, K.E. Van Wingerden, K. Nooter, Met.-Based
Drugs 5 (1998) 179.
[15] C. Pettinari, Main Group Met. Chem. 22 (1999) 661.
[16] S.P. Fricker (Ed.), Metal Compounds in Cancer Therapy, Chapman & Hall,
London, UK, 1994, pp. 147–179.
[17] A.K. Saxena, F. Huber, Coord. Chem. Rev. 95 (1989) 109.
[18] J. Susperregui, M. Bayle, G. Lain, C. Giroud, T. Baltz, G. Deleris, Eur. J. Med.
Chem. 34 (1999) 617.
[19] L. Pellerito, L. Nagy, Coord. Chem. Rev. 224 (2002) 111.
[20] T.S. Basu Baul, W. Rynjah, E. Rivarola, A. Lycka, M. Holcapek, R. Jirasko, D. de
Vos, R.J. Butcher, A. Linden, J. Organomet. Chem. 691 (2006) 4850.
[21] L. Tian, Y. Sun, H. Li, X. Zheng, Y. Cheng, X. Liu, B. Qian, J. Inorg. Biochem. 99
(2005) 1646.
In addition, the cytotoxic activities of the previously reported
titanocene complexes bearing similar ligands presented IC50 values
from 24 to 175
lM [36–38] which are much lower than those
[22] G. Han, P. Yang, J. Inorg. Biochem. 91 (2002) 230.
found in the cyclopentadienyltin(IV) derivatives with IC50 values
from 0.037 to 0.384 lM.
ˇ
ˇ
ˇ
´
´
[23] S. Gómez-Ruiz, G.N. Kaluderovic, S. Prashar, E. Hey-Hawkins, A. Eric, Z. Zizak,
Z.D. Juranic´, J. Inorg. Biochem. 102 (2008) 2087.
[24] M.N. Xanthopoulou, S.K. Hadjikakou, N. Hadjiliadis, M. Schurmann, K.
Jurkschat, A. Michaelides, S. Skoulika, T. Bakas, J.J. Binolis, S. Karkabounas, K.
Charalabopoulos, J. Inorg. Biochem. 96 (2003) 425.
4. Conclusions
[25] M.N. Xanthopoulou, S.K. Hadjikakou, N. Hadjiliadis, E.R. Milaeva, J.A. Gracheva,
V.-Y. Tyurin, N. Kourkoumelis, K.C. Christoforidis, A.K. Metsios, S. Karkabounas,
K. Charalabopoulos, Eur. J. Med. Chem. 43 (2008) 327.
[26] M.N. Xanthopoulou, S.K. Hadjikakou, N. Hadjiliadis, M. Kubicki, S. Skoulika, T.
Bakas, M. Baril, I.S. Butler, Inorg. Chem. 46 (2007) 1187.
[27] M.N. Xanthopoulou, S.K. Hadjikakou, N. Hadjiliadis, N. Kourkoumelis, E.R.
Milaeva, J.A. Gracheva, V.-Y. Tyurin, I.I. Verginadis, S. Karkabounas, M. Baril, I.S.
Butler, Rus. Chem. Bull. 56 (2007) 767.
[28] C. Ma, Q. Jiang, R. Zhang, Appl. Organomet. Chem. 17 (2003) 623.
[29] C. Ma, J. Zhang, Appl. Organomet. Chem. 17 (2003) 788.
[30] F. Barbieri, F. Sparatore, R. Bonavia, C. Bruzzo, G. Schettini, A. Alama, J. Neuro-
Oncol. 60 (2002) 109.
A variety of cyclopentadienyltin(IV) compounds have been syn-
thesized and structurally characterized. Metal derivatives, were
tested in vitro against human tumour cell lines 8505C anaplastic
thyroid cancer, A253 head and neck tumour, A549 lung carcinoma,
A2780 ovarian cancer and DLD-1 colon carcinoma. The studied
tin(IV) compounds presented very high activity against the evalu-
ated tumoural cell lines, up to ca. 100 times higher than that of cis-
platin and up to ca. 5000 times higher than those reported for
similar cyclopentadienyltin(IV) derivatives [32].
3 (which contains the tetramethylcyclopentadienyl ligand) is
the most active compound against all the studied cancer cells, pre-
senting IC50 values between 0.037 and 0.085 lM.
Following on from these results, intensive studies on the mech-
anism of action of cyclopentadienyltin(IV) derivatives against the
different studied cancer cells are currently being carried out.
[31] E.R.T. Tiekink, Appl. Organometal. Chem. 22 (2008) 533.
[32] B. Gleeson, J. Claffey, D. Ertler, M. Hogan, H. Müller-Bunz, F. Paradisi, D. Wallis,
M. Tacke, Polyhedron 27 (2008) 3619.
[33] P.M. Abeysinghe, M.M. Harding, Dalton Trans. (2007) 3474.
[34] K. Strohfeldt, M. Tacke, Chem. Soc. Rev. 37 (2008) 1174.
[35] C.G. Hartinger, P.J. Dyson, Chem. Soc. Rev. 38 (2009) 391.
ˇ
ˇ
ˇ
[36] S. Gómez-Ruiz, G.N. Kaluderovic´, D. Polo-Cerón, S. Prashar, M. Fajardo, Z. Zizak,
´
Z.D. Juranic, T.J. Sabo, Inorg. Chem. Commun. 10 (2007) 748.
[37] S. Gómez-Ruiz, G.N. Kaluderovic´, S. Prashar, D. Polo-Cerón, M. Fajardo, Z. Zizak,
ˇ
ˇ
ˇ
´
T.J. Sabo, Z.D. Juranic, J. Inorg. Biochem. 102 (2008) 1558.
ˇ
ˇ
ˇ
[38] S. Gómez-Ruiz, G.N. Kaluderovic´, Z. Zizak,
I. Besu, Z.D. Juranic´, S. Prashar, M.
Supplementary data
Fajardo, J. Organomet. Chem. 694 (2009) 1981.
ˇ
ˇ
ˇ
[39] D. Pérez-Quintanilla, S. Gómez-Ruiz, Z. Zizak, I. Sierra, S. Prashar, I. del Hierro,
M. Fajardo, Z.D. Juranic´, G.N. Kaluderovic´, Chem. Eur. J. 15 (2009) 5588.
[40] S. Gómez-Ruiz, S. Prashar, M. Fajardo, A. Antiñolo, A. Otero, J. Organomet.
Chem. 692 (2007) 3057.
CCDC 729606, 729607 and 729608 contain the supplementary
crystallographic data for 1, 2 and 4, respectively. These data can
be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/
retrieving.html, or from the Cambridge Crystallographic Data Cen-
tre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-
033; or e-mail: deposit@ccdc.cam.ac.uk.
[41] S. Gómez-Ruiz, D. Polo-Cerón, S. Prashar, M. Fajardo, A. Antiñolo, A. Otero, Eur.
J. Inorg. Chem. (2007) 4445.
[42] A. Antiñolo, I. López-Solera, I. Orive, A. Otero, S. Prashar, A.M. Rodríguez, E.
Villaseñor, Organometallics 20 (2001) 71.
[43] C.E. Zachmanoglou, A. Docrat, B.M. Bridgewater, G. Parkin, C.G. Brandow, J.E.
Bercaw, C.N. Jardine, M. Lyall, J.C. Green, J. Am. Chem. Soc. 124 (2002) 9525.
[44] SCALE3 ABSPACK: Empirical Absorption Correction, CrysAlis – Software package,
Oxford Diffraction Ltd., 2006.
[45] G.M. Sheldrick, SHELXS-97, Program for Crystal Structure Solution, Göttingen,
1997.
[46] G.M. Sheldrick, SHELXL-97, Program for the Refinement of Crystal Structures,
Göttingen, 1997.
[47] P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. McMahon, D. Vistica, J.T.
Warren, H. Bokesch, S. Kenney, M.R. Boyd, J. Natl. Cancer Inst. 82 (1990)
1107.
[48] H. Schumann, L. Esser, J. Loebel, A. Dietrich, Organometallics 10 (1991) 2585.
[49] H. Wiesenfeldt, A. Reinmuth, E. Barsties, K. Evertz, H.-H. Brintzinger, J.
Organomet. Chem. 369 (1989) 359.
Acknowledgements
We gratefully acknowledge financial support from the Ministe-
rio de Educación y Ciencia, Spain (Grant no. CTQ2008-05892/BQU)
and Ministerium für Wirtschaft und Arbeit des Landes Sachsen-An-
halt, Deutschland (Grant No. 6003368706). We would also like to
thank Ioana Grosu (Universität Leipzig) for her help in the prepara-
tion of samples for mass spectrometry.
[50] P. Jutzi, R. Dickbreder, Chem. Ber. 119 (1986) 1750.
[51] C. Alonso-Moreno, A. Antiñolo, I. López-Solera, A. Otero, S. Prashar, A.M.
Rodriguez, E. Villaseñor, J. Organomet. Chem. 656 (2002) 129.
[52] S. Xu, X. Dai, B. Wang, X. Zhou, J. Organomet. Chem. 645 (2002) 262.
[53] R. Fernández, E. Carmona, Eur. J. Inorg. Chem. (2005) 3197.
[54] D. del Río, A. Galindo, I. Resa, E. Carmona, Angew. Chem. Int. Ed. 44 (2005)
1244.
[55] I. Resa, E. Carmona, E. Gutiérrez-Puebla, A. Monge, Science 305 (2004) 1136.
[56] M. Conejo, R. Fernández, D. del Río, E. Carmona, A. Monge, C. Ruiz, A.M.
Márquez, J.F. Sanz, Chem. Eur. J. (2003) 4452.
References
[1] Medicinal inorganic chemistry, Chem. Rev. (Special Thematic Issue) 99 (1999).
[2] J.L. Sessler, S.R. Doctrow, J. McMurry, S.J. Lippard (Eds.), Medicinal Inorganic
Chemistry, American Chemical Society Symposium Series 903, American
Chemical Society, Washington DC, 2005.
[3] M. Gielen, E.R.T. Tiekink, Metallotherapeutic Drugs and Metal-Based
Diagnostic Agents: The Use of Metals in Medicine, Wiley, Chichester, 2005.
[4] M. Gielen (Ed.), Tin-Based Anti-Tumor Drugs, Springer-Verlag, Berlin, 1990.
[5] M. Gielen, Coord. Chem. Rev. 151 (1996) 41.
[57] R. Fernández, I. Resa, D. del Río, E. Carmona, E. Gutiérrez-Puebla, A. Monge,
Organometallics 22 (2003) 381.
[6] P. Yang, M. Guo, Coord. Chem. Rev. 185–186 (1999) 189.

S. Gómez-Ruiz et al. / Polyhedron 29 (2010) 16–23
23
[58] M.M. Conejo, R. Fernández, D. del Río, E. Carmona, A. Monge, C. Ruiz, Chem.
Commun. (2002) 2916.
[62] A. Antiñolo, M. Fajardo, S. Gómez-Ruiz, I. López-Solera, A. Otero, S. Prashar,
Organometallics 23 (2004) 4062.
[59] M.M. Conejo, R. Fernández, E. Gutiérrez-Puebla, A. Monge, C. Ruiz, E. Carmona,
Angew. Chem. Int. Ed. 39 (2000) 1949.
[60] P. Jutzi, Chem. Rev. 86 (1986) 983.
[61] A. Antiñolo, M. Fajardo, S. Gómez-Ruiz, I. López-Solera, A. Otero, S. Prashar,
A.M. Rodríguez, J. Organomet. Chem. 683 (2003) 11.
[63] S. Gómez-Ruiz, S. Prashar, M. Fajardo, A. Antiñolo, A. Otero, M.A. Maestro, V.
Volkis, M.S. Eisen, C.J. Pastor, Polyhedron 24 (2005) 1298.
[64] O.R. Allen, A. L Gott, J.A. Hartley, J.M. Hartley, R.J. Knox, P.C. McGowan, Dalton
Trans. (2007) 5082.