Syntheses, structural characterization and in vitro cytotoxic activity of triorganotin(IV) complexes based on 1,7-dihydroxycarbonyl-1,7-dicarba-closo- dodecaborane ligand

Article abstract of DOI:10.1016/j.jorganchem.2013.04.039

Seven novel triorganotin(IV) compounds containing m-CDC^2- (m-CDCH₂ = 1,7-dihydroxycarbonyl-1,7-dicarba-closo-dodecaborane) have been synthesized and structural characterized. The central tin atoms are five-coordinated to assume a distorted trigonal bipyramidal configuration not only in the binuclear monomers 1, 3 and 4 but also in the polymers 2, 5, 6 and 7. It was observed that complexes 3, 4 and 5 could be obtained only in the presence of the ancillary carboxylate ligands, 2,3-pyrazinedicarboxylic acid, 2-pyridinecarboxylic acid and 2,6-pyridinedicarboxylic acid, respectively. The reaction of m-CDCH₂ with (n-Bu₃Sn)₂O in the presence of the bridging ligands 4,4'-bipyridine and 4,4'-vinylenedipyridine afforded one-dimensional coordination polymers 6 and 7, respectively. Most of the complexes exhibit higher cytotoxic activities than cis-platin against two cancer cell lines, K-562 and Hela.

Full text of DOI:10.1016/j.jorganchem.2013.04.039

Journal of Organometallic Chemistry 740 (2013) 1e9
Contents lists available at SciVerse ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Syntheses, structural characterization and in vitro cytotoxic activity
of triorganotin(IV) complexes based on 1,7-dihydroxycarbonyl-1,7-dicarba-closo-
dodecaborane ligand
*
*
Huaiwei Wang, Dacheng Li, Min Hong , Jianmin Dou
Shandong Provincial Key Laboratory of Chemical Energy Storage and Novel Cell Technology, School of Chemistry and Chemical Engineering, Liaocheng University,
Liaocheng 252059, China
a r t i c l e i n f o
a b s t r a c t
Seven novel triorganotin(IV) compounds containing m-CDC2ꢀ (m-CDCH2 ¼ 1,7-dihydroxycarbonyl-1,7-
dicarba-closo-dodecaborane) have been synthesized and structural characterized. The central tin
atoms are five-coordinated to assume a distorted trigonal bipyramidal configuration not only in the
binuclear monomers 1, 3 and 4 but also in the polymers 2, 5, 6 and 7. It was observed that complexes
Article history:
Received 21 February 2013
Received in revised form
19 April 2013
Accepted 25 April 2013
3,
4 and 5 could be obtained only in the presence of the ancillary carboxylate ligands, 2,3-
pyrazinedicarboxylic acid, 2-pyridinecarboxylic acid and 2,6-pyridinedicarboxylic acid, respectively.
The reaction of m-CDCH2 with (n-Bu3Sn)2O in the presence of the bridging ligands 4,40-bipyridine and
4,40-vinylenedipyridine afforded one-dimensional coordination polymers 6 and 7, respectively. Most of
the complexes exhibit higher cytotoxic activities than cis-platin against two cancer cell lines, K-562
and Hela.
Keywords:
Organotin(IV)
1,7-Dihydroxycarbonyl-1,7-dicarba-closo-
dodecaborane
X-ray crystallography
In vitro cytotoxic activity
Ó 2013 Elsevier B.V. All rights reserved.
1. Introduction
organotin(IV) species have been reported, shedding more light on
the issue of drug design.
Cisplatin and other platinum species belong to the blockbusters
of anticancer drug sold worldwide. However, remaining problems
such as severe side effects and resistance phenomena trigger an
increasing demand for novel innovative drugs with a mode of action
differing from that of the platinum generation of cancer chemo-
therapeutics [1e3]. In recent years especially, organotin(IV) com-
plexes have attracted major attention due to their structural variety
(ranging from monomer to polymer, from linear to pentagonal-
bipyramid and even beyond) [4] and far more diverse stereochem-
istry than platinum derivatives, and by rational ligand design, pro-
vide control over key kinetic properties (such as hydrolysis rate of
ligands) [5]. Furthermore, they are kinetically stable and relatively
lipophilic. Because of these fundamental differences compared to
“classical coordination metal complexes”, organotin(IV) complexes
offer ample opportunities in the design of novel classes of medicinal
compounds, potentially with new metal-specific modes of action
[1,6,7]. Interestingly, many highly promising results with novel
The polyhedral boron clusters “carboranes” have extensive ap-
plications in the pharmaceuticals (such as for boron neutron cap-
ture therapy) [8e11]. A series of amine-carboxyboranes and
polyhedral hydroborate salts were tested for their anti-neoplastic-
cytotoxic activity [12e15]. Hall et al. observed that a number of
compounds exhibited cytotoxicity in single cell suspended tumors
(leukemia and Hela-S3) and not surprisingly, the substituents off
the carboranes dramatically influenced the observed ED50 values in
a given screen. However, in general, they were not as potent as
metal complexes with copper, cobalt, iron or chromium derivatives
[16e18] or the heterocyclic amine-carboxyboranes [19].
Several carboxylate derivatives of tin based on 1,2- or 1,7-
dicarba-closo-dodecaborane have also been reported [20e24], in
which the carborane cage is linked to the carboxylic moiety via a
boron or carbon atom. Studies reveal that these carborane-based
organotin compounds present lower in vitro antitumor activities
than the clinically used methatrexate and doxorubicin, but higher
than 5-fluorouracil, cis-platin and carboplatin. Currently, the best
known and most investigated carboranes are the three 12-vertex
ortho, meta, and para isomers C2B10H12, dicarbo-closo-dodeca
boranes. Here, we first report the syntheses, characterization and
in vitro cytotoxic activities of a series of novel triorganotin dicar-
boxylate derivatives of 1,7-dihydroxycarbonyl-1,7-dicarba-closo-
* Corresponding authors. Tel.: þ86 635 8239795, þ86 635 8230662; fax: þ86 635
8239001.
E-mail addresses: hongminlcu@163.com (M. Hong), dougroup@163.com
(J. Dou).
0022-328X/$ e see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jorganchem.2013.04.039

2
H. Wang et al. / Journal of Organometallic Chemistry 740 (2013) 1e9
dodecaborane. It is expected that the biological activities of orga-
notin(IV) compounds could be enhanced by the introduction of
carborane, which would afford more opportunities for designing
new antitumor drugs with higher activity.
the coordination of organotin(IV) compounds. We failed to obtain
complexes 3e5 when the reactions were carried out in the absence
of the ancillary ligands. About this phenomenon, it may result from
the adjustment of the pH values by adding the ancillary carboxylic
acids, which may be favorable to the formation of carborane
carboxylate organotin(IV) compounds. Meanwhile, the carborane
carboxylic acid may have a higher competitiveness than the
ancillary ligand due to its earlier into the chemical reaction, and the
specific reason is unclear. The synthesis procedures of complexes
1e7 are summarized in Scheme 1.
2. Results and discussion
2.1. Syntheses
All complexes were prepared with different methods under
atmospheric conditions. Complexes 1e6 are colorless crystals, and
complex 7 is a light red crystalline solid. All compounds except for
complex 2 are stable in air. It is interesting that complexes 3e5 can
be obtained in the presence of the ancillary carboxylic acid ligands,
2,3-pyrazinedicarboxylic acid, 2-pyridinecarboxylic acid or 2,6-
pyridinedicarboxylic acid, respectively, which are not involved in
2.2. IR spectra
The IR spectra of complexes 1e7 were recorded in the range of
4000e400 cmꢀ1. The stretching frequencies of interest are those
associated with COO-, SneC, SneN and SneO groups. The strong
Scheme 1. The reaction procedures.

H. Wang et al. / Journal of Organometallic Chemistry 740 (2013) 1e9
3
absorption in the region 430e490 cmꢀ1, which is absent in the
spectrum of the free ligand, is assigned to the SneO stretching
mode. Also, the strong absorption bands that appear at 1600e
1670 cmꢀ1 and 1330e1390 cmꢀ1 in these spectra are assigned to
the asymmetric and symmetric vibrations of the COOꢀ moiety,
respectively. All these values are consistent with those detected in a
number of organotin(IV)-oxygen derivatives [25].
2.3. NMR spectra
The 1H NMR spectra show that the signals of the eCO2H proton
in the spectrum of the ligands are absent in these complexes,
indicating the removal of the eCO2H proton and the formation of
SneO bond. The information well accords with what the IR data
have revealed. The 13C NMR spectra of all complexes show a sig-
nificant downfield shift of all carbon resonances compared with the
free ligands because of an electron-density transfer from the li-
Fig. 1. Molecular structure of complex 1 (the additional carbon atoms of the Sne
Phenyl groups are omitted for clarity).
gands to the metal atoms. The single resonance at
d
¼ 165.78e
by three phenyl groups (1 and 3) or three methyl groups (4). The
mean axial angles OeSneO, 173.1ꢁ (1), 175.8ꢁ (3) and 175.7ꢁ (4),
suggest that these structures are nearly ideal trigonal bipyramid.
Two types of SneO bonds are present in these complexes: a short
166.99 ppm are attributed to the COOꢀ groups in complexes 1e7.
These data are consistent with the structures of 1e7.
119Sn NMR chemical shifts of tin complexes appear to depend on
not only the coordination number, but also the type of donor atoms
ꢀ
ꢀ
distance ranging from 2.151 A to 2.219(18) A and a longer distance
bonding to the metal ion. The
may be used to give tentative indications of the coordination
environment around tin atoms in the solution. The values for
d
values for 119Sn NMR chemical shift
ꢀ
lying in the range of 2.376e2.50 A, which are close to that reported
in other triorganotin carboxylates [29,30].
d
In their supramolecular structures, the tin-coordinated meth-
anol molecules and the water molecules play a crucial role, since
each of them participates in an intermolecular hydrogen bond with
oxygen atom of the carboxylate group in their structures. For
complexes 1 and 3, the discrete molecules can form the 2D network
supramolecular structures (Supporting information, Fig. S1 for 1
and Fig. S2 for 3) via OeH/O]C intermolecular hydrogen-bonding
interactions (shown in Table 2). In complex 4, the two monomers
interact with each other via hydrogen-bonding interactions to form
a 20-membered hydrogen-bonding ring and a 44-membered
hydrogen-bonding ring, resulting in the construction of supramo-
lecular network together (Fig. S3).
119Sn NMR chemical shifts of triphenyltin complexes 1e3 exhibit a
single sharp resonance at ꢀ86.5 ppm, ꢀ99.6 ppm and ꢀ85.5 ppm,
respectively, which are consistent with the range for tetrahedral
geometry [20,26]. The 119Sn NMR chemical shifts show a single
resonance at 172.17 and 162.97 ppm for trimethyltin(IV) complexes
4 and 5, and for tributyltin(IV) compounds 6 and 7 at 146.50 and
143.41 ppm, all of which are characteristic of the four-coordinated
triorganotin(IV) compounds [27]. Obviously, solution 119Sn NMR
spectra of these compounds are different from the five-coordinated
tin centers determined by the X-ray crystal structural analysis,
especially for coordination polymers 5e7. For compounds 1e5, the
collapse of the intermolecular interactions existing in the solid
state could result from the rupture of the weaker SneO bond with
longer bond length observed in their crystal structures. These
weaker SneO bonds are formed by the R3Sn moiety and the coor-
dinated solvent molecules MeOH or H2O in compounds 1, 3 and 4,
or by the R3Sn moiety and the carboxyl group in compounds 2 and
5. But for compounds 6 and 7, the bond length of SneN [2.527(6) Å,
2.4.2. Crystal structures of complexes 2 and 5
Both complexes 2 and 5 are ionic compounds, in which the
organotin(IV) carboxylate anions are counteracted by the triethy-
lammonium cations. The repeating unit, the 1D infinite chain and
ꢀ
ꢀ
2.564(6) A and 2.528(7) A] determined by X-ray crystal diffraction
is longer than that of the conventional SneN bonds, such as in the
ꢀ
triorganotin(IV) pyridinecarboxylates, at about 2.2e2.3 A [28], and
the rupture of SneN bonds results in the four-coordinated tir-
organotin(IV) monomeric species in the solution.
2.4. Description of crystal structures
2.4.1. Crystal structures of complexes 1, 3 and 4
For these three complexes, the molecular structures are illus-
trated in Figs. 1e3, respectively; selected bond lengths and bond
angles for these complexes are given in Table 1. They are all discrete
molecules and have similar structures. Complex 1 is a discrete
binuclear structure. Complexes 3 and 4 both own two monomers in
a crystal unit. Two kinds of monomers in complex 3 are different
due to one water molecule coordinated to Sn(2), which is different
from the coordination environment of the other tin atoms in
complex 3. In contrast to this, the structures of two monomers in
complex 4 are the same. The geometries around Sn atoms in these
complexes are trigonal bipyramidal with the axial positions being
occupied by two oxygen donor atoms from the carboxylate and the
methanol or water molecule. The equatorial planes were taken up
Fig. 2. Molecular structure of complex 3 (the additional carbon atoms of the Sne
Phenyl groups are omitted for clarity).

4
H. Wang et al. / Journal of Organometallic Chemistry 740 (2013) 1e9
Table 2
Hydrogen bonding geometries for complexes 1e6.
DeH/A
d (H/A)
d (D/A)
<(DHA)
Complex 1
O(6)eH(60)/O(2)#1
O(5)eH(5A)/O(4)#2
Complex 2
2.05
1.88
2.701(10)
2.645(9)
135.5
155.5
N(1)eH(1A)/O(4)#3
Complex 3
1.91(11)
2.798(10)
164(9)
O(1)eH(1)/O(5)#2
O(6)eH(6A)/O(3)#3
O(9)eH(90)/O(8)#4
Complex 4
1.99
1.88
1.87
2.654(12)
2.726(12)
2.656(13)
138.0
173.4
159.9
O(1)eH(1E)/O(9)#1
O(6)eH(6A)/O(11)#2
O(7)eH(7C)/O(3)#3
O(12)eH(12D)/O(5)#4
Complex 5
1.80
1.85
1.80
1.87
2.62(3)
2.66(3)
2.61(3)
2.66(3)
171.8
167.1
170.1
164.3
N(1)eH(1A)/O(6)#3
Complex 6
C(37)eH(37)/O(4)#3
1.96(19)
2.27
2.84(2)
163(12)
148.0
3.094(9)
Symmetry code: (#1 for 1) ꢀxþ1, yþ1/2, ꢀzþ1/2; (#2 for 1) ꢀx, yþ1/2, ꢀzþ1/2; (#3
for 2) ꢀxþ2/3, ꢀyþ4/3, ꢀzþ1/3; (#2 for 3) xꢀ1/2, yþ1/2, z; (#3 for 3) xþ1/2, yþ1/2,
z; (#4 for 3) ꢀxþ3/2, yꢀ1/2, ꢀzþ1/2; (#1 for 4) xꢀ1/2, ꢀyþ1/2, zþ1; (#2 for 4) x, y,
zþ1; (#3 for 4) x, yꢀ1, zꢀ1; (#4 for 4) xþ1/2, ꢀyþ1/2, zꢀ1; (#3 for 5) x, yꢀ1, zþ1; (#3
for 6) x, yþ1, z.
Fig. 3. Molecular structure of complex 4.
the 2D supramolecular structure of complex 2 are illustrated in
Figs. 4 and 5 and Fig. S4, respectively. The repeating unit, the
ladder-shaped structure and the 3D supramolecular structure of
complex 5 are shown in Figs. 6 and 7 and Fig. S5, respectively.
Selected bond lengths and bond angles for these complexes are
listed in Table 3. In complex 2, the dicarboxylate ligand acts a
connector and binds two successive triphenyltin atoms, which re-
sults in the formation of the 1D chain. In complex 5, the trime-
thyltin(IV) groups are linked by the deprotonated m-CDCH2 ligand,
which affords the formation of 1D chain. Further, two chains are
connected along the opposite direction by the bidentate carboxyl-
ates coordinating to the trimethyltin(IV) groups, which gives rise to
a ladder-shaped structure. As can be seen from Fig. 7, four ligands
are linked by four metal centers into a 24-membered macrocycle,
triethylammonium cations, (Et3NH)þ, link two chains by the
intermolecular NeH/O and CeH/O hydrogen-bonding in-
teractions resulting in the formation of supramolecular structures
of complexes 2 and 5 (Fig. S4 for 2 and Fig. S5 for 5).
2.4.3. Crystal structures of complexes 6 and 7
The X-ray crystal structures of 6 and 7, which are both 1D co-
ordination polymers, are shown in Fig. 8a and b, respectively. The
salient metric parameters of 6 and 7 are summarized in Table 4. In
these complexes the dominant structure-directing role appears to
be that of the ancillary ligand which alternates with the dicar-
boxylate ligands in a bridging coordination mode to form chain
structures. The coordination polymers 6 and 7 represent interesting
examples comprised of three distinct building blocks: (a) two
tributyltin units; (b) a carboranedicarboxylate that bridges the two
tin units and (c) a ditopic ligand containing two terminal nitrogen
donor centers that interconnect the Sn2/m-CDC motifs. The geom-
etry around tin is a trigonal-bipyramid, where the equatorial po-
sitions are occupied by three n-butyl groups and the axial positions
are shared by an oxygen donor atom from the carboxylate ligand
and a nitrogen donor atom from the pyridine ligand. The mean Sne
ꢀ
ꢀ
with a sort of cavity with width of 7.795 Ae10.678 A.
In complexes 2 and 5, tin atom is trigonal bipyramidal (C3O2
coordination environment), with the apical positions being taken
up by the oxygen atoms of two different deprotonated m-CDCH2
ligands. The average of apical angle OeSneO of complexes 2 and 5
are 179.03ꢁ and 177.6ꢁ, respectively, which suggests that the
structures are near to an ideal trigonal bipyramid. In complex 2,
there exists only one type of SneO bond with the distance of
ꢀ
ꢀ
2.234(4) A and 2.246(4) A, and in complex 5, the distances of SneO
ꢀ
ꢀ
bond range from 2.154 A to 2.461 A, which are close to those re-
ported in other triorganotin carboxylates [31e33].
ꢀ
ꢀ
N bond lengths for 6 and 7 are 2.546 A and 2.528 A, respectively,
which are consistent with those reported in other triorganotin
carboxylates [34].
Analyses of the supramolecular structures in the crystal lattice
of complexes 2 and 5 reveal that the triethylammonium cations
play important roles in the supramolecular arrangements. The
Table 1
ꢁ
ꢀ
Selected bond lengths [A] and angles [ ] for complexes 1, 3 and 4.
1
3
4
Sn(1)eO(1)
Sn(1)eO(6)
Sn(2)eO(3)
Sn(2)eO(5)
O(1)eSn(1)eO(6)
O(3)eSn(2)eO(5)
2.153(7)
2.424(7)
2.161(6)
2.417(6)
176.1(3)
170.1(2)
Sn(1)eO(2)
Sn(1)eO(1)
Sn(2)eO(4)
Sn(2)eO(6)
Sn(3)eO(7)
Sn(3)eO(9)
O(4)eSn(2)eO(6)
O(2)eSn(1)eO(1)
2.173(8)
2.413(8)
2.150(8)
2.392(8)
2.151(9)
2.376(9)
175.4(3)
176.2(3)
Sn(1)eO(1)
Sn(1)eO(2)
Sn(2)eO(6)
Sn(2)eO(4)
Sn(3)eO(8)
Sn(3)eO(7)
Sn(4)eO(10)
Sn(4)eO(12)
O(2)eSn(1)eO(1)
O(4)eSn(2)eO(6)
O(8)eSn(3)eO(7)
O(10)eSn(4)eO(12)
2.494(19)
2.219(18)
2.50(2)
2.182(17)
2.167(18)
2.40(2)
2.169(18)
2.41(2)
174.4(7)
176.7(8)
175.3(8)
176.2(7)

H. Wang et al. / Journal of Organometallic Chemistry 740 (2013) 1e9
5
Fig. 4. Repeating unit of complex 2 (the additional carbon atoms of the SnePhenyl
groups are omitted for clarity).
In their crystal structures, the 1D polymers of 6 interact with
each other by two different CeH/O supramolecular interactions
ꢀ
ꢀ
[C(10)eH(10B)/O(2) 3.334 A] and [C(37)eH(37)/O(4) 3.094 A].
The hydrogen atoms (H10B, H37) involved in CeH/O interactions
belong to the butyl moiety and pyridine moiety, respectively, and
the oxygen atoms (O2, O4) are derived from the deprotonated m-
CDCH2 ligand. Together, these interactions generate a 3D supra-
molecular architecture (Fig. S6a). The complex 7 is also a 1D coor-
dination polymer whose structure is similar to that of 6; however,
its supramolecular assembly is different. Analysis of the supramo-
lecular structure in the crystal lattice of 7 reveals that supramo-
Fig. 6. Repeating unit of complex 5.
same complex against different cell lines present a high selectivity.
Generally, the higher activity is usually observed for the K-562
tumor cells and the lower one for the Hela tumor cells.
ꢀ
lecular interactions [C(20)eH(20)/O(2) 3.489 A] (C20 derived
from the pyridine ligand) play important roles in the supramolec-
ular arrangements. The 1D polymers of 7 interact with each other
On the basis of the data analysis, possible structureeactivity
relationships could be outlined. According to the previous reports,
the organo-ligand R bound with tin atom plays an important role
for their biological activities [37,38], and usually in the condition of
the same coordination structures, the anticancer activity of tri-
organotin(IV) complexes follows the trend of Bu > Ph > Me, which
can also be proved in our present work, that is 2 > 5 for both two
tumor cells. But for the different molecular structures, the in vitro
cytotoxic activity would be influenced by several factors. For
example, the triphenyltin derivative 2 exhibits higher activity than
the tributyltin(IV) complexes 6 and 7, which may be due to the form
via this interaction to form
(Fig. S6b).
a 3D supramolecular structure
2.5. In vitro cytotoxic activity
All compounds were screened for the preliminary in vitro
cytotoxic activity studies on two different cell lines: chronic
myeloid leukemia cell line (K562) and cervical cancer cell line
(Hela), at five different concentrations ranging from 10 to 0.1 mM in
DMSO. Relevant activities could be noted for all complexes in these
two cell lines. The observed IC50 values with the exception of
complexes 1 and 3 due to their bad solubility are listed in Fig. 9.
These results are in good agreement with other reports on bioactive
organotin(IV) species, which reached activities in the low micro-
molar range [6,7,20].
of zwitterion for complex 2 [39]. From the inhibition [%] of 10 mM
samples we can also see that with the similar coordination envi-
ronment, the triphenyltin complexes 1 and 3 are more active than
the trimethyltin complex 4.
Although both complexes 1 and 3 are low soluble, they exhibit
higher activity compared with the other complexes. This encour-
aging cytotoxic activity may make complexes 1 and 3 be suitable
candidates for further modification to improve their solubility
which may influence the cytotoxicity. This research work is in
progress in our laboratories.
Because most of the complexes showed inhibition activity at
concentration of >10
at concentration of 10
m
M, we herein merely listed biological results
M in Table 5 for the sake of discussing the
m
structureeactivity relationship. But for complexes 1 and 3, owing to
the partially solubility in DMSO, the top clear solution of the pre-
Further chemical and pharmacological studies will be necessary
to unravel a structureeactivity relationship, from which novel
organotin antitumor drugs with possible clinical applications can
be developed.
pared 10
mM samples were used to determine their in vitro cyto-
toxicity. The inhibition [%] of triphenyltin (IV) complexes 1 and 3 at
the unknown concentration (<<10 mM) against human tumor cells
are listed in Table 6.
The results of in vitro cytotoxic effects demonstrate these
complexes are active against two tumor cell lines (K562 and Hela)
and generally exhibit higher activity than cisplatin [35,36], the
clinically widely used drug. Also, the inhibitory potencies of the
Fig. 5. 1D chain structure of complex 2 (the additional carbon atoms of the SnePhenyl
groups are omitted for clarity).
Fig. 7. Ladder-shaped structure of complex 5.

6
H. Wang et al. / Journal of Organometallic Chemistry 740 (2013) 1e9
Table 3
Table 4
ꢁ
ꢁ
ꢀ
ꢀ
Selected bond lengths [A] and angles [ ] for complexes 2 and 5.
Selected bond lengths [A] and angles [ ] for complexes 6 and 7.
2
5
6
7
Sn(1)eO(3)
Sn(1)eO(1)
O(1)eSn(1)eO(3)
2.246(4)
2.234(4)
179.03(15)
Sn(1)eO(1)
Sn(1)eO(3)
Sn(2)eO(7)
Sn(2)eO(4)
Sn(3)eO(2)
Sn(3)eO(5)
O(1)eSn(1)eO(3)
O(7)eSn(2)eO(4)
O(5)eSn(3)eO(2)
2.236(7)
2.250(7)
2.161(8)
2.461(8)
2.453(7)
2.154(7)
176.9(4)
178.3(4)
177.5(3)
Sn(1)eO(1)
Sn(1)eN(1)
Sn(2)eO(3)
Sn(2)eN(2)
O(1)eSn(1)eN(1)
O(3)eSn(2)eN(2)
2.170(5)
2.527(6)
2.184(5)
2.564(6)
172.08(19)
166.23(17)
Sn(1)eO(1)
Sn(1)eN(1)
O(1)eSn(1)eN(1)
2.174(6)
2.528(7)
176.3(2)
with the carboxylate ligand in a bridging coordination mode to
form chain structures.
Complexes 2, 4, 5, 6 and 7 display high in vitro cytotoxic activ-
ities against chronic myeloid leukemia cell line (K-562) and cervical
cancer cell line (Hela). For the triorganotin(IV) complexes, the
zwitterion triphenyltin derivatives 2 exhibit the highest activity.
Therefore, we can see that the cytotoxic activity would be affected
by both the organic ligand R and their molecular structures. Also,
the methyltin compounds still show the lowest activity. The ob-
tained results allow the recognition of preliminary structureeac-
tivity relationships, but the definite trend could yet be established.
These bi- or multi-nuclear compounds with carborane ligand
represent a new paradigm for tin-based antitumor complexes and
appear to offer a great potential as new anticancer agents.
3. Conclusion
In conclusion, this contribution has shown that the reactions of
m-CDCH2 with triphenyl, trimethyl, and bis(tri-n-butyl)tin oxide
moieties give either discrete or polymeric structures. The tin atoms
in these complexes are Lewis acid and can form additional bonds to
coordinating solvent molecules such as water, methanol molecule
and pyridine.
It could be suggested that both the volume of the organic sub-
stituents attached to the tin atoms and the reaction solvent have an
influence on the molecular structure and the supramolecular
arrangement of the complexes. The reaction of m-CDCH2 with tri-
phenyltin chloride in the presence of methanol solvent afforded
two discrete molecular compounds 1 and 3 while in the presence of
aprotic solvents afforded the 1D chain complex 2. In contrast to the
reactions of m-CDCH2 with triphenyltin, that involving trimethyltin
chloride afforded a ladder coordination polymer 5 in the presence
of 2,6-pyridinedicarboxylic acid, and complex 4 have a similar
structure with complex 3 in the presence of 2-pyridinecarboxylic
acid. If a third component is used in the reaction m-CDCH2 with
(n-Bu3Sn)2O in the form of the ancillary ligands, 4,40-bipyridine and
4,40-vinylenedipyridine, 1D coordination polymers 6 and 7 are
obtained. In these two reactions the dominant structureedirecting
role appears to be that of the ancillary ligands which alternates
4. Experimental details
4.1. Materials and measurements
Triphenyltin chloride, trimethyltin chloride, bis(tri-n-butyl)tin
oxide, triethylamine and solvents were commercially available and
were used without further purification. The 1,7-dihydroxycarbonyl-
1,7-dicarba-closo-dodecaborane was prepared according to the
literature method [40]. The melting points were obtained with a
Kofler micro melting point apparatus and are uncorrected.
Elemental analyses were performed with a PE-2400II apparatus.
Infrared spectra were recorded with a Niclet-5700 spectrometer
using KBr discs and NaCl optics. 1H, 13C, and 119Sn NMR spectra were
recorded with a Varian Mercury Plus 400 spectrometer operating at
400, 100.6, and 149.2 MHz, respectively. The spectra were acquired
at room temperature (298 K), unless otherwise specified. The
chemical shifts are reported in ppm with respect to the references
and are stated relative to external tetramethylsilane (TMS) for 1H
Fig. 8. (a) 1D polymeric structure of 6. (b) 1D polymeric structure of 7 (the additional
carbon atoms of the Snebutyl groups are omitted for clarity).
Fig. 9. In vitro cytotoxicity of complexes 2 and 4e7 against cancer cells K-562 and
Hela. Data represent mean ꢂ SD of three independent experiments.

H. Wang et al. / Journal of Organometallic Chemistry 740 (2013) 1e9
7
Table 5
temperature. After three weeks the colorless block crystals
Inhibition [%] of triorganotin(IV) complexes 2 and 4e7 [dose level of 10.0
against human tumor cells.
mM]
were obtained. Yield: 71%. M.P. 125e127 ꢁC. Anal. Calc. for
C
124H140B30O18Sn6: C 50.40, H 4.78%; Found: C 50.16, H 4.97%. IR
(KBr, cmꢀ1): nas(COO), 1648.9; ns(COO), 1384;
(SneC), 543.3; (Sne
O), 453.1. 1H NMR (CDCl3, ppm):
3.46 (s, 12H, eCH3), 1.46 (s, 4H,
H2O), 1.16 (s, 4H, eOH), 7.43e7.63 (m, 90H, Ph). 13C NMR (CDCl3,
NO
Compound
K-562
Hela
n
n
2
4
5
6
7
{[(C2H5)3NH]þ$[(Ph3Sn)(m-CDC)]ꢀ
[(Me3Sn)2(m-CDC)(CH3OH)2]
}
n
85.65
69.39
73.98
82.97
82.91
84.41
65.30
68.83
90.38
77.67
d
{[(C2H5)3NH]þ$[(Me3Sn)3(m-CDC)2]ꢀ}n
[(Bu3Sn)2(m-CDC)(4,40-bipy)]n
[(Bu3Sn)2(m-CDC)(4,40-bpe]n
ppm): d 166.16 (COO); 128.57e136.54 (PheC); 76.58, 76.90 (C-1 and
C-7); 50.73 (CH3OHeC). 119Sn NMR (CDCl3, ppm):
d
ꢀ85.50.
4.2.4. [(Me3Sn)2(m-CDC)(CH3OH)2] (4)
m-CDCH2 (23.2 mg, 0.10 mmol) and triethylamine (0.2 mmol,
20.2 mg) were dissolved in 20 ml CH3OH. After 10 min the trime-
thyltin chloride (39.9 mg, 0.2 mmol) was added to the solution
and then 2-pyridinecarboxylic acid (12.3 mg, 0.1 mmol) was added
to the resulting solution after half an hour. The reaction was
lasted 20 h and the filtrate was allowed to evaporate slowly at room
temperature. After two weeks the colorless block crystals
were obtained. Yield: 79%. M.P. 214e216 ꢁC. Anal. Calc. for
and 13C NMR and to neat tetramethyltin for 119Sn NMR. The 13C and
119Sn NMR spectra were determined in the decoupling mode.
4.2. Syntheses of complexes 1e7
4.2.1. [(Ph3Sn)2(m-CDC)(CH3OH)2] (1)
A mixture of m-CDCH2 (23.2 mg, 0.10 mmol), triethylamine
(0.2 mmol, 20.2 mg) and triphenyltin chloride (77.1 mg, 0.2 mmol)
in 20 ml CH3OH was sealed in a Teflon-lined bomb and heated to a
temperature of 80 ꢁC for 2 days, then cooled slowly to room tem-
perature. The filtrate was allowed to evaporate slowly at room
temperature. After two weeks colorless crystals suitable for X-ray
diffraction were obtained. Yield: 82%. M.P. 154e156 ꢁC. Anal. Calc.
for C42H48B10O6Sn2: C 50.73, H 4.87%; Found: C 50.45, H 5.02%. IR
C
12H36B10O6Sn2: C 23.54, H 5.83%; Found: C 23.73, H 5.63%. IR (KBr,
cmꢀ1): nas(COO), 1631.3; ns(COO), 1354.3;
(SneC), 555.2; (SneO),
477.3. 1H NMR (CDCl3, ppm):
1.25 (s, 2H, eOH), 3.07 (s, 6H, eCH3),
0.88 (s, 18H, SneCH3). 13C NMR (CDCl3, ppm):
166.290 (COO); 8.19
(CH3); 76.67, 76.87 (C-1 and C-7); 50.61 (CH3OHeC). 119Sn NMR
(CDCl3, ppm): 172.17.
n
n
d
d
d
(KBr, cmꢀ1): nas(COO), 1606.9; ns(COO), 1384.4;
O), 453.8. 1H NMR (CDCl3, ppm):
3.49 (s, 6H, eCH3), 1.26 (s, 2H, e
OH), 7.62e7.66 (m, 30H, Ph). 13C NMR (CDCl3, ppm):
166.15 (COO);
128.26e136.80 (PheC); 76.61, 76.93 (C-1 and C-7); 50.52 (CH3OHe
C). 119Sn NMR (CDCl3, ppm):
ꢀ86.5.
n(SneC), 544; n(Sne
4.2.5. {[(C2H5)3NH]þ$[(Me3Sn)3(m-CDC)2]ꢀ}n (5)
d
m-CDCH2 (23.2 mg, 0.10 mmol), and triethylamine (0.2 mmol,
20.2 mg) were dissolved in 20 ml CH3OH. After 10 min the trime-
thyltin chloride (39.9 mg, 0.2 mmol) was added to the solution and
then 2,6-pyridinedicarboxylic acid (16.7 mg, 0.1 mmol) was added
to the resulting solution after half an hour. The reaction was lasted
20 h and the filtrate was allowed to evaporate slowly at room
temperature. After three weeks the colorless block crystals were
obtained. M.P. 208e210 ꢁC. Yield. 61%. Anal. Calc. for
d
d
4.2.2. {[(C2H5)3NH]þ$[(Ph3Sn)(m-CDC)]ꢀ}n (2)
The m-CDCH2 (23.2 mg, 0.1 mmol) was added to the solution of
benzene together with triethylamine (0.2 mmol, 20.2 mg), and the
mixture was stirred for 10 min. After the addition of triphenyltin
chloride (77.1 mg, 0.2 mmol), the mixture was reacted at 50 ꢁC for
10 h and then filtered. The solvent was gradually removed by
evaporation under vacuum until a solid product was obtained. The
obtained solid was then recrystallized from dichloromethane/
hexane (v/v ¼ 3:1), and colorless crystals of complex 2 were
recovered. Yield: 63%. M.P. 116e118 ꢁC. Anal. Calc. for
C
23H63B20NO8Sn3: C 26.21, H 6.02, N 1.33%; Found: C 26.46, H 5.90,
N 1.42%. IR (KBr, cmꢀ1): nas(COO), 1623.6; ns(COO), 1383.7;
(SneC),
545.4; 1.26 (t, 9H, eCH3),
(SneO), 453.9. 1H NMR (CDCl3, ppm):
3.06 (m, 6H, eCH2). 0.88 (s, 27H, SneCH3). 13C NMR (CDCl3, ppm):
166.99 (COO); 8.28 (CH3); 76.54, 76.86 (C-1 and C-7). 119Sn NMR
(CDCl3, ppm): 162.97.
n
n
d
d
d
4.2.6. [(Bu3Sn)2(m-CDC)(4,40-bipy)]n (6)
C
28H41B10NO4Sn: C 49.28, H 6.06, N 2.05%; Found: C 48.99, H 6.22, N
2.19%. IR (KBr, cmꢀ1): nas(COO), 1639.8; ns(COO), 1349;
(SneC),
544.6; 1.24 (t, 9H, eCH3),
(SneO), 455.4. 1H NMR (CDCl3, ppm):
3.02 (q, 6H, eCH2). 7.64e7.66 (m, 15H, Ph). 13C NMR (CDCl3, ppm):
165.86 (COO); 128.979e136.00 (PheC); 76.60, 76.91 (C-1 and C-7).
119Sn NMR (CDCl3, ppm):
ꢀ99.6.
n
A mixture of 0.10 mmol (n-Bu3Sn)2O, m-CDCH2 (23.2 mg,
0.10 mmol) and 4,40-bipy (19.2 mg, 0.10 mmol) was heated under
reflux in a mixture of toluene and ethanol (10 ml, v/v ¼ 3:2) for 6 h
affording a clear solution. The reaction mixture was filtered and the
solvent was removed in vacuo to afford a white solid product. The
single crystals of 6 were obtained by the slow evaporation of
CH3CN/Acetone solution of product. Yield: 79%. M.P. 128e130 ꢁC.
Anal. Calc. for C38H72B10N2O4Sn2: C 47.22, H 7.51, N 2.90%; Found: C
47.52, H 7.31, N 2.71%. IR (KBr, cmꢀ1): nas(COO), 1655.1; ns(COO),
n
d
d
d
4.2.3. {[(Ph3Sn)2(m-CDC)(CH3OH)2]$[(Ph3Sn)2(m-CDC)(H2O)
(CH3OH)]2} (3)
m-CDCH2 (23.2 mg, 0.10 mmol), and triethylamine (0.2 mmol,
20.2 mg) were dissolved in 20 ml CH3OH. After 10 min the tri-
phenyltin chloride (77.1 mg, 0.2 mmol) was added to the solution
and then 2,3-pyrazinedicarboxylic acid (17.6 mg, 0.1 mmol) was
added to the resulting solution after half an hour. The reaction was
lasted 20 h and the filtrate was allowed to evaporate slowly at room
1383.7;
(CDCl3, ppm):
0.93 (t, 18H, butyl CH3), 1.27e1.37 (m, 12H, butyl eCH2e), 1.55e1.70
(m, 24H, butyl SneCH2eCH2e). 13C NMR (CDCl3, ppm):
165.78
n(SneC), 544.1;
n(SneO), 464.9, n
(SneN), 454.3. 1H NMR
d
7.54 (d, 4H, bipy), 8.74e8.76 (d, 4H, bipy), 0.89e
d
(COO); 13.80, 17.11, 27.04, 27.74 (butyl-C); 76.57, 76.89 (C-1 and C-
7); 150.57, 145.73, 121.59 (bipy-C). 119Sn NMR (CDCl3, ppm):
d
146.50.
Table 6
Inhibition [%] of triphenyltin(IV) complexes 1 and 3 at the unknown concentration
[below dose level of 10.0 mM] against human tumor cells.
4.2.7. [(Bu3Sn)2(m-CDC)(4,40-vinylenedipyridine)]n (7)
A mixture of 0.10 mmol (n-Bu3Sn)2O, m-CDCH2 (23.2 mg,
0.10 mmol) and 4,40-vinylenedipyridine (18.2 mg, 0.10 mmol) was
heated under reflux in a mixture of toluene and ethanol (10 ml, v/
v ¼ 3:2) for 6 h affording a clear solution. The reaction mixture was
filtered and the solvent was removed in vacuo to afford a white
NO
Compound
K-562
Hela
1
3
[(Ph3Sn)2(m-CDC)(CH3OH)2]
{[(Ph3Sn)2(m-CDC)(CH3OH)2]$
[(Ph3Sn)2(m-CDC)(H2O)(CH3OH)]2}
85.20
86.06
84.33
88.27

8
H. Wang et al. / Journal of Organometallic Chemistry 740 (2013) 1e9
Table 7
Crystallographic data and structure refinement parameters for complexes 1e7.
Complex
1
2
3
4
5
6
7
Empirical formula
M
C42H48B10O6Sn2
994.28
Monoclinic
P2(1)/c
21.0601(18)
12.5639(12)
7.9351(15)
90
100.8090(10)
90
C28H41B10NO4Sn
682.41
Trigonal
R-3
26.889(3)
26.889(3)
29.512(3)
90
90
120
18 478(4)
18
1.104
C124H140B30O18Sn6 C12H36B10O6Sn2
C23H63B20NO8Sn3 C38H72B10N2O4Sn2 C20H37B5NO2Sn
2954.80
Monoclinic
C2/c
20.7520(17)
13.4129(11)
49.497(4)
90
621.89
Orthorhombic
Pna2(1)
19.1982(18)
20.724(2)
14.0643(13)
90
1054.01
Triclinic
P-1
966.46
Triclinic
P-1
496.25
Monoclinic
C2/c
Crystal system
Space group
ꢀ
a [A]
10.6775(10)
14.3346(15)
17.2197(17)
70.9890(10)
88.096(2)
77.1150(10)
2426.9(4)
2
9.8105(4)
9.8194(6)
26.9493(11)
92.342(4)
99.540(3)
109.152(5)
2405.8(2)
2
10.7386(9)
21.536(2)
23.474(2)
90
94.7770(10)
90
ꢀ
b [A]
ꢀ
c [A]
a
b
g
[ꢁ]
[ꢁ]
[ꢁ]
93.8440(10)
90
90
90
3
ꢀ
V [A ]
4661.4(7)
4
1.417
13746.3(19)
4
5595.7(9)
8
5409.8(9)
8
Z
Dcalc (Mg/m3)
1.428
1.476
1.442
1.334
1.219
m
[mmꢀ1
]
1.115
0.650
1.134
1.807
1.570
1.075
0.958
F (000)
1992
6264
5912
2448
1044
992
2040
Crystal size (mm)
Reflections collected
Independent reflections
Rint
0.48 ꢃ 0.26 ꢃ 0.17 0.45 ꢃ 0.42 ꢃ 0.39 0.45 ꢃ 0.22 ꢃ 0.21 0.30 ꢃ 0.21 ꢃ 0.18 0.41 ꢃ 0.32 ꢃ 0.15 0.32 ꢃ 0.28 ꢃ 0.21 0.39 ꢃ 0.22 ꢃ 0.19
22 918
38 838
34 812
28 253
12 347
17 211
13 430
8202
7192
12 057
9774
8414
8502
4757
0.0431
0.0632
0.0677
0.0698
0.0507
0.0481
0.0500
Goodness-of-fit on F2
1.057
0.858
1.149
1.078
1.017
1.081
1.096
R1[I > 2
wR2[I > 2
s
(I)], R1 (all data)
0.0637, 0.1802
0.0654, 0.1561
0.1027, 0.1817
0.0997, 0.1953
0.1386, 0.2160
0.0836, 0.2169
0.1649, 0.2725
0.0723, 0.1929
0.1032, 0.2171
0.0592, 0.1419
0.0753, 0.1532
0.0650, 0.1853
0.1146, 0.2424
s
(I)], wR2 (all data) 0.1086, 0.2337
solid product. The light red single crystals of 7 were obtained by the
slow evaporation of CH3CN/Acetone solution of product. Yield: 79%.
M.P. 149e151 ꢁC. Anal. Calc. for C20H37B5NO2Sn: C 48.40, H 7.51, N
2.82%; Found: C 48.10, H 7.62, N 2.62%. IR (KBr, cmꢀ1): nas(COO),
complexes) DMSO solution was added and further incubation was
carried out at 37 ꢁC for 48 h. The compounds were serially diluted
(in four to six steps) with DMSO and added to cell incubation
medium at the final concentration of 0.1
20 l of 5 mg/mL of MTT mixture was added to each well. After 4 h
incubation, the culture medium was removed, and 50 l of iso-
mM DMSO in the medium.
1662.7; ns(COO), 1337.6;
n
(SneC), 545.0;
n
(SneO), 467.1,
n
(SneN),
m
452.1. 1H NMR (CDCl3, ppm):
d
7.26 (s, 1H, eCH]CHe), 7.40 (d, 2H,
m
bpe), 8.63 (d, 2H, bpe), 0.87e0.90 (t, 9H, butyl CH3), 1.24e1.34 (m,
propanol was added to dissolve the insoluble blue formazan pre-
cipitates produced by MTT reduction. The plate was shaken for
20 min on a plate shaker to ensure complete dissolution. The op-
tical density of each well was measured at 570 nm wavelength. The
cytotoxic activity was determined three times in independent
experiments.
6H, butyl eCH2e), 1.57e1.74 (b, 12H, butyl SneCH2eCH2e). 13C
NMR (CDCl3, ppm): d 165.80 (COO); 13.83,17.20, 27.03, 27.75 (butyl-
C), 46.16; 76.80, 76.90 (C-1 and C-7); 150.57, 143.66, 130.78, 121.39
(bpe-C). 119Sn NMR (CDCl3, ppm):
d 143.41.
Hela cell lines (90
concentration of about 10 000e15 000 cells/ml and were incubated
in an atmosphere of 5% CO2 for 24 h. Then 10 l of tested agents
ml) were seeded into 96 well plates at a
4.3. X-ray crystallography studies
m
The crystals of complexes 1e7 were mounted in Lindemann
either complete culture medium (control wells) or drug concen-
trations diluted in complete culture medium (test wells) was added
and further incubation was carried out at 37 ꢁC for 48 h. Drug
cytotoxic was measured by means of SRB colorimetric assay. Cul-
ture medium was removed via downward tapping and 10% cold
(4 ꢁC) trichloroacetic acid (TCA) was gently added to the wells.
Microplates were left for 30 min at 4 ꢁC, washed five times with tap
water and left to dry at room temperature for at least 24 h. Sub-
capillaries under nitrogen. Diffraction data were collected with a
Brucker Smart CCD area detector with graphite-monochromated
ꢀ
Mo K
a
radiation (
l
¼ 0.71073 A). A semiempirical absorption
correction was applied to the data. The structure was solved by
direct methods using SHELXS-97 and refined against F2 by full-
matrix least-squares using SHELXS-97. Hydrogen atoms were
placed in calculated positions. Crystal data and experimental de-
tails of the structure determinations are listed in Table 7.
sequently, 100 ml of 4 mg/ml sulforhodamine B in 1% acetic acid
solution was added to each well and left at room temperature for
20 min. SRB was removed and the plates were washed five times
with 1% acetic acid before air drying. Bound SRB was solubilized
4.4. Pharmacology
4.4.1. Cell lines and culture conditions
with 150 ml of unbuffered Tris-base solution and plates were left on
The human tumor cell lines, chronic myeloid leukemia cell line
(K-562) and cervical cancer cell line (Hela), which were used for
screening, were grown and maintained in RPMI-1640 and MEM
medium, respectively, supplemented with 10% fetal bovine serum
at 37 ꢁC in humidified incubators in an atmosphere of 5% CO2.
a plate shaker for at least 10 min. The optical density of each well
was measured at 515 nm wavelength. The cytotoxic activity was
determined three times in independent experiments.
Acknowledgments
4.4.2. Cytotoxicity assays
The authors thank the National Natural Science Foundation of
China (20971063) for financial supported.
K-562 and Hela cell proliferation in compound-treated cultures
were evaluated by using a system based on the tetrazolium com-
pound (MTT) and sulforhodamine B (SRB) methods, respectively, in
the School of Medicine and Pharmacy, Ocean University of China. K-
Appendix A. Supplementary material
562 cell lines (90
tration of about 10 000e15 000 cells/mL and were incubated in an
atmosphere of 5% CO2 for 24 h. Then, 10 l of the sample (organotin
ml) were seeded into 96 well plates at a concen-
CCDC 8533849 (1), 889839 (2), 889840 (3), 889842 (4), 889841
(5), 889843 (6) and 889844 (7) contain the supplementary
m

H. Wang et al. / Journal of Organometallic Chemistry 740 (2013) 1e9
9
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