Synthesis, characterization and biological activity of antimony(III)

or bismuth(III) chloride complexes with dithiocarbamate ligands

derived from thiuram degradation
I.I. Ozturk
a,b,
, C.N. Banti
b
, N. Kourkoumelis
c,
, M.J. Manos
d
, A.J. Tasiopoulos
d
, A.M. Owczarzak
e
,
M. Kubicki
e
, S.K. Hadjikakou
b,
a
Department of Chemistry, Namk Kemal University, 59030 Tekirdag, Turkey
b
Section of Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
c
Medical Physics Laboratory, Medical School, University of Ioannina, 45110 Ioannina, Greece
d
Department of Chemistry, University of Cyprus, Nicosia, Cyprus
e
Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland
a r t i c l e i n f o
Article history:
Received 14 June 2013
Accepted 22 August 2013
Available online 4 September 2013
Keywords:
Bioinorganic chemistry
Antimony(III) and bismuth(III) complexes
Polymorphs
Structure activity relationship (SAR)
Cytotoxicity
PCA
Molecular docking
a b s t r a c t
Antimony(III) or bismuth(III) complexes of formulae {[SbCl(Me
2
DTC)
2
]
n
} (1), {[BiCl(Me
2
DTC)
2
]
n
} (2) and
{[Bi(Et
2
DTC)
3
]
2
} (3) (Me
2
DTCH = dimethyldithiocarbamate, C
3
H
7
NS
2
and Et
2
DTCH = diethyldithiocarba-
mate, C
5
H
11
NS
2
) were isolated from the reactions between SbCl
3
or BiCl
3
with tetramethylthiuram mono-
sulde (Me
4
tms), tetramethylthiuram disulde (Me
4
tds) or tetraethylthiuram disulde (Et
4
tds). In the
case of 1 two polymorphs were isolated depending on the synthetic procedure followed. Crystal growth
from the reaction of antimony(III)chloride with Me
4
tms in methanol produced 1a polymorph, while
those derived from Me
4
tds in acetonitrile/dichloromethane produced 1b form. The complexes 13 were
characterized by m.p., e.a., FT-IR, FT-Raman,
1
H,
13
C NMR spectroscopy and Thermal GravimetryDiffer-
ential Thermal Analysis (TGADTA). Moreover, single crystal X-ray diffraction analysis was carried out for
1a, 1b, 2 and 3. X-ray powder diffraction data conrm the existence of one polymorph in the bulk of each
sample of 1a and 1b.
1
H NMR spectra in the DMSO-d
6
solutions of 1a and 1b suggest the retention of the
structural variations. Complexes 1 and 2 are polymers with distorted square pyramidal (SPY) geometry in
each monomeric unit. The known structure of 3 was re-determined to be used for the theoretical and
structure activity relationship studies (SAR).
Complexes 13 were evaluated for their in vitro cytotoxic activity against human breast adenocarci-
noma (MCF-7) and human cervix adenocarcinoma (HeLa) cells. Complex 3 is more active against HeLa
cells whereas 1a, 1b and 2 against MCF-7. Compound 1a shows slightly higher activity than 1b. Principal
components analysis (PCA) was performed to discriminate the signicant physicochemical molecular
descriptors while regression analysis successfully related the experimental inhibitory concentration,
(IC
50
) to the independent variables indexed by PCA. The calculated IC
50
values are satisfactorily compared
with the measured inhibitory activity of the complexes.
2013 Elsevier Ltd. All rights reserved.
1. Introduction
The bis(N,N-dialkylthiocarbamoyl)sulde and bis(N,N-dial-
kylthiocarbamoyl)disulde derivatives, (thiuram suldes or
thiuram disuldes) of the general formula R
2
NC(S)S
n
C(S)NR
2
are
the thiocarbamoyl esters of dialkyldithiocarbamic acids [1]. The
biological applications of thiuram disuldes varied within a broad
spectrum. Thiuram disuldes (R
4
tds) have been used as fungicides,
as therapy against alcoholism, and as arrestors of human immu-
nodefciency virus infections such as AIDS [14]. Studies on the
thiuram monosuldes (R
4
tms), on the other hand, are rare [5].
Thiuram monosuldes inhibit peptidyl-prolyl cis/trans isomerase
activity, in HeLa cells. Flow Cytometry Data Analysis (FACS)
showed that thiuram monosuldes induce G
0
arrest of the
HCT116 cells. These results suggest that thiuram monosuldes
have the potential to guide the development of novel anticancer
drugs [5].
Reactions of thiuram monosuldes or disuldes lead to three
different categories of products: (a) adducts; (b) thiuram oxidation
products and (c) ligand reduction with concomitant degradation to
dithiocarbamate and/or thiocarboxamide ligands (Fig. 1) [6].
0277-5387/$ - see front matter 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.poly.2013.08.052

Corresponding authors at: Department of Chemistry, Namk Kemal University,

59030 Tekirdag, Turkey (I.I. Ozturk), Medical Physics Laboratory, Medical School,
University of Ioannina, Ioannina, Greece (N. Kourkoumelis), Section of Inorganic and
Analytical Chemistry, Department of Chemistry, University of Ioannina, Greece.
Tel.: +30 26510 08374; fax.:+ 30 26510 08786 (S.K. Hadjikakou).
E-mail addresses: iiozturk@nku.edu.tr (I.I. Ozturk), nkourkou@uoi.gr
(N. Kourkoumelis), shadjika@uoi.gr (S.K. Hadjikakou).
Polyhedron 67 (2014) 89103
Contents lists available at ScienceDirect
Polyhedron
j our nal homepage: www. el sevi er . com/ l ocat e/ pol y
Examples of thiuram monosuldes or disuldes adducts
(Fig. 1a), include the complexes: [Zn(Me
4
tms)I
2
] (Me
4
tms: Tetram-
ethylthiuram monosulde) [7], [Hg(Et
4
tds)I
2
] (Et
4
tds: Tetraethyl-
thiuram disulde) [8a], [CuCl(Me
4
tms)]
2
, [CuBr(Me
4
tms)]
n
,
[CuI(Me
4
tms)]
2
, [CuCl(Et
4
tms)] (Et
4
tms: Tetraethylthiuram mono-
sulde) [8b]. Besides, ve membered dicationic cyclic derivatives
which are neutralized by metal halides counter anions (Fig. 1b)
may obtained; e.g. [Et
4
biit-3]
2+
[Hg
2
I
6
]
2
(Et
4
biit-3: 3,5-bis(N,
N
0
diethylimonium)-1,2,4-trithiolane) [9a], [Et
4
biit-3]
2+
2[FeCl
4
]

and [Bu
4
biit-3]
2+
[Cu
2
X
6
]
2
(Bu
4
biit-3: 3,5-bis(N,N
0
dibutylimoni-
um)-1,2,4-trithiolane, X:Cl, Br) [9b]. In the case of ligands degrada-
tion (Fig. 1c), the SS bond are cleaved resulting in the formation of
dithiocarbamate and/or thiocarboximade fragments. These frag-
ments can then coordinate to metal ions. Examples of ligand reduc-
tion with simultaneous ligand degradation include: Tl(Me
2
dtc)
3
[10a], [Me
3
Sb(dtc)
2
] [10b], [V
2
(l-S
2
)
2
(Et
2
dtc)
4
] [10c], [Mo(R
2
dtc)
4
]
(R: Me, Et, Ph) [10df], [Cu(Et
2
dtc)]
4
and [Cu{(i-Pr)
2
dtc}Br
2
] [8b].
Dithiocarbamates, on the other hand, already play an important
role in medicine, as antidotes in heavy-metal detoxication [11].
Dithiocarbamates exhibit strong tendency for metal ions com-
plexetion with a variety of coordination modes (Fig. 2), especially
with antimony(III) and bismuth(III) [12,13].
Metaldithiocarbamate complexes have also been investigated
for their anti-cancer potential, most notably with platinum(IV) pal-
ladium(II), tin(IV) and gold(I/III) [11]. Diethyldithiocarbamates can
inhibit tumor induction caused by benzo[a]pyrene [11]. Recently,
the bismuth diethyldithiocarbamate complex Bi(Et
2
DTC)
3
was
shown to be a potent in vitro cytotoxin against seven human cancer
cell lines: (i) breast cancer (MCF-7, estrogen receptor (ER)+/proges-
terone receptor (PgR)+), (ii) breast cancer (EVSA-T, estrogen recep-
tor (ER)/progesterone receptor (PgR), (iii) renal cancer (A498),
(iv) non-small cell lung cancer (H226), (v) ovarian cancer (IGROV),
(vi) melanoma (M19 MEL) and (vii) colon cancer (WIDR) [11]. The
complex Bi(S
2
CNEt
2
)
3
shows selective activity towards MCF-7 (ER
positives) cells [11]. The steroid receptors (ER-a and ER-b) are lo-
cated in human breast cancer cells (MCF-7), since estrogen recep-
tors (ERs) are expressed in human breast cancer [14a]. This sex
steroid plays an important role in the development and propaga-
tion of the disease [14a]. ERs are also of special interest because
their protein levels are elevated in premalignant and malignant
breast lesions as opposed to normal tissue [14b]. Consequently,
inhibition of the ERs has become one of the major strategies for
the prevention and treatment of breast cancer [14b]. In contrast
HeLa cells are devoid of estrogen receptors (ERs) [14c].
In the progress of our research on the design and development
of new metallotherapeutics containing metal ions of group 15 [15],
we have synthesized and characterized new antimony(III) and bis-
muth(III) chloride complexes with the tetramethylthiuram mono-
sulde (Me
4
tms), tetramethylthiuram disulde (Me
4
tds) and
tetraethylthiuram disulde (Et
4
tds) ligands (Fig. 3). Reactions of
thiuram suldes with antimony(III) and bismuth(III) chlorides lead
to the ligand degradation with the simultaneous formation of the
complexes 13. Thus, tetramethylthiuram monosulde (Me
4
tms)
and tetramethylthiuram disulde (Me
4
tds) react with anti-
mony(III) chloride to form two different polymorphs of formula
{[SbCl(Me
2
DTC)
2
]
n
} (1a and 1b). Bismuth(III) chloride on the other
hand, reacts with Me
4
tds or Et
4
tds to produce {[BiCl(Me
2
DTC)
2
]
n
}
(2) and {[Bi(Et
2
DTC)
3
]
2
} (3) complexes. Complexes 13 have been
characterized by a variety of analytical methods; FT-IR, FT-Raman,
1
H,
13
C NMR, TGADTA, X-ray powder diffraction (XRPD) and sin-
gle crystal X-ray diffraction (XRD) analysis. Although, the crystal
structure of 3 has been deposited four times up to now [16], how-
ever, its structure was re-determined for the subsequent theoreti-
cal and structure activity relationship studies (SAR). Compounds
13 were also tested for in vitro cytotoxicity against human breast
adenocarcinoma (MCF-7) and human cervix adenocarcinoma
(HeLa) cell lines. The high activity observed for the known com-
pound 3 against MCF-7, (estrogen receptor (ER)+/progesterone
receptor (PgR)+) (IC
50
= 6 nM), and EVSA-T, (estrogen receptor
(ER)/progesterone receptor (PgR)) (IC
50
= 9 nM), [11] prompted
us to undertake a comparison study with 1a, 1b and 2. Multivariate
statistical and regression analysis were employed in order to eval-
uate the experimental activity results in relation to conformation
related molecular descriptors.
2. Results and discussion
2.1. General aspects
Complex 1 was derived by two different routes which lead to
two polymorphs (1a and 1b): reacting tetramethylthiuram mono-
sulde with antimony(III) chloride in methanol solution (1a) or by
reacting tetramethylthiuram disulde with antimony(III) chloride
in acetonitrile/dichloromethane solutions (1b) in 1:1 ligand to me-
tal ratio (Scheme 1). 2 was obtained when bismuth(III) chloride
was used instead of SbCl
3
under the same conditions (Scheme 1).
In contrast, 3 was isolated only by reacting methanol solutions of
tetraethylthiuram disulde with bismuth(III) chloride in 1:1 ligand
S
S
S
N N
R
R
R
R
M
M
S
S S
S
N
R
R
R
R S S
S
NR
2
R
2
N
2+
[MX
n
]
2-
(a) (c) (b)
Fig. 1. Possible products obtained from the reactions of thiuram suldes with metal ion; (a) adduct; (b) thiuram oxidation products and (c) products derived from ligand
reduction with concomitant degradation to dithiocarbamates and/or thiocarboxamides.
N
R
R
S
S
M N
R
R
S
S
M N
R
R
S
S M
N
R
R
S
S
M
M
Isobidentate Anisobidentate Monodentate Triconnective
Fig. 2. Possible coordination modes to a metal ion of the dialkyldithiocarbamate ligands.
90 I.I. Ozturk et al. / Polyhedron 67 (2014) 89103
to metal molar ratio (Scheme 1). During this reaction the SS or C
S bonds are clipped and dithiocarbamate and/or thiocarboximade
fragments formed coordinate to the metal ions.
The products 13, were characterized by e.a.; FT-IR, FT-Raman,
1
H,
13
C NMR, TGADTA, XRPD and single crystal by X-ray diffrac-
tion crystallography. Crystals of complex 3 were found to be iden-
tical with those already reported [16]. Compound 3 crystallized in
P2
1
/c space group with a = 12.3965(8), b = 13.5006(8), c =
14.7833(9) and b = 99.942(6), while the crystal data of those
previous reported are: space group P2
1
/c with a = 12.55,
b = 13.58, c = 14.86 and b = 100.2 [16a]; space group P2
1
/a with
a = 14.825(4), b = 13.640(2), c = 12.605(3) and b = 100.01(3)
[16b]; space group P2
1
/c with a = 12.625(2), b = 13.628(3),
c = 14.835(3) and b = 100.002(2) [16c]; space group P2
1
/c with
a = 12.4824(6), b = 13.5486(7), c = 14.7668(7) and b = 99.979(1)
[16d].
The solubility of the complexes 1a and 1b in DMSO/H
2
O (0.5%
DMSO in water) was checked by UVVis spectroscopy (Fig. S1).
The stability of 1a and 1b in DMSO-d
6
solutions was conrmed
by
1
H NMR spectra (Fig. S2). Slight changes between the initial
1
H NMR spectra and those after 48 h were probably due to solva-
tion effects (Fig. S2 inset). The thermal stability of complexes 13
S
S
S
N N
CH
3
CH
3
CH
3
H
3
C
S
S N S
S
N
CH
3
H
3
C
CH
3
CH
3
S
S N S
S
N
CH
2
H
2
C
H
2
C
H
2
C
H
3
C
H
3
C C H
3
CH
3
Tetramethylthiuram monosulfide
(Me
4
tms, C
6
H
12
N
2
S
3
)
Tetramethylthiuram disulfide
(Me
4
tds, C
6
H
12
N
2
S
4
)
Tetraethylthiuram disulfide
(Et
4
tds, C
10
H
20
N
2
S
4
)
Fig. 3. Precursors used in this work.
S
S
S
N N
CH
3
CH
3
CH
3
H
3
C
Me
4
tms
+ MCl
3
S
S
N
H
3
C
H
3
C
M
S
S
N
CH
3
CH
3
Cl
M= Sb, (1)
M= Bi, (2)
1: M=Sb; MeOH
2: M=Bi;
MeOH/MeCN
S
S N S
S
N
CH
3
H
3
C
CH
3
CH
3
Me
4
tds
+ MCl
3 2: M=Bi;
MeOH/MeCN
S
S N S
S
N
CH
2
H
2
C
H
2
C
H
2
C
H
3
C
H
3
C CH
3
CH
3
Et
4
tds
+BiCl
3
S
S N
CH
2
H
2
C
H
3
C
H
3
C
S
S N
H
2
C
H
2
C
CH
3
CH
3
Bi
S S
N
H
2
C CH
2
CH
3
CH
3
(3)
MeOH
1: M=Sb;
MeCN/CH
2
Cl
2
Scheme 1. Reactions scheme for the synthesis of 14.
I.I. Ozturk et al. / Polyhedron 67 (2014) 89103 91
was also tested by TG-DTA analysis (under nitrogen ow). The data
shows that compounds 13 remain stable up to 154 (1), 185 (2)
and 145 (3) C, while beyond this temperature decomposition oc-
curs by endothermic steps 154319 (1), 185328 (2) and 145
415 (3) C, respectively (see SI, Figs. S3S5).
2.2. Vibrational spectroscopy
Signicant vibrational bands are listed in Table 1 (Figs. S6S16).
The characteristic IR bands that are sensitive to molecular struc-
ture are the stretching modes for the m(CN), m(CS), m(MS) and
m(MCl) bands (M = Sb or Bi) [15]. The IR spectra of complexes show
distinct vibrational bands at 1528 (1), 1519 (2) and 1508 (3) cm
1
respectively, which are attributed to the m(CN) vibrations and at
964882 cm
1
(1), 965879 cm
1
(2) and 982841 cm
1
(3) which
are assigned to the m(CS) vibrations. The IR spectra of complexes 1
3 show two m(CS) vibration bands and one strong m(CN) band. This
is an indication of the anisobidentate character of the S
2
CNR
2
li-
gands [17]. The corresponding m(CN) and m(CS) vibration bands of
the free ligands are found at 15171499, 962 and 861 cm
1
for
Me
4
tms, 1498, 978 and 848 cm
1
for Me
4
tds and 1496, 999 and
817 cm
1
for Et
4
tds, respectively [18].
Far-IR spectra of 1 and 2 show distinct vibration bands at 304
and 423 cm
1
, which are assigned to m(SbCl) and m(BiCl) [6
7,15,19]. The m(SbS) vibration band at 384 cm
1
(1) [15] and the
m(BiS) vibration bands are 202 cm
1
for complex 2 and 247 cm
1
for complex 3, respectively [19].
Vibration bands m(MS) and m(MCl) (M: Sb or Bi) are also Ra-
man active [15,20]. Thus, bands at 183 and 229 cm
1
in the Raman
spectra of complexes 2 and 3 are due to the m(BiS) vibrations [20],
while the band at 448 cm
1
is assigned to the m(BiCl) vibration for
complex 2 [20]. The m(SbS) vibration band in the Raman spectrum
is at 388 cm
1
while the m(SbCl) vibration band is 310 cm
1
for
complex 1.
2.3. NMR spectroscopy
The
1
H and
13
C NMR spectral data of 13 and of free ligands
Me
4
tms, Me
4
tds and Et
4
tds have been recorded in DMSO-d
6
on a
Bruker AC250 MHz FT NMR spectrometer (Figs. S17S28). Signi-
cant resonances are summarized in Table 2. The
1
H NMR spectral
of 1a and 1b in DMSO-d
6
are also recorded on a Bruker Avance
AV-500 MHz LC NMR spectrometer. The resonance signal for the
methyl protons, of 1a and 1b complexes is at 3.352 (1a) and
3.355 (1b) ppm respectively, while the singlet at 3.415 ppm is
due to DMSO-d
6
. The differences observed for the methyl protons
in the case of 1a and 1b (Fig. 4) suggest the retention of the struc-
tural variations in solution as well.
The
13
C NMR spectra of Me
4
tms and Me
4
tds ligands show sig-
nals at 186.98 ppm and 192.60 ppm, respectively, due to the
>C(@S) carbons. The
13
C(NCS
2
) resonance signals in the
13
C NMR
spectra of 13 are observed at 197.03, 200.82 and 198.99 ppm,
respectively compared to similar dithiocarbamate complexes. The
methyl carbons were observed at 44.24 ppm (1), 44.16 ppm (2)
and 12.95 ppm (3), respectively. The signal at 48.74 ppm in the
spectrum of 3 is assigned to the methylene carbon.
2.4. Crystal and molecular structure {[SbCl(Me
2
DTC)
2
]
n
} (1a and 1b),
{[BiCl(Me
2
DTC)
2
]
n
} (2) and {[Bi(Et2DTC)
3
]
2
} (3)
Selected bond distances and angles of complexes 1a, 1b and 2
are given in Table 3, while their ORTEP diagrams are shown in Figs. 5
7.
Two polymorphs of 1 were isolated, 1a and 1b (Figs. 5 and 6)
depending on the preparative procedure followed. Crystals from
Table 1
Vibrational (IR, far-IR and Raman) spectra data (cm
1
) of complexes 13 and the corresponding ones of the ligands that complexes 13 derived.
Compound Far-IR Raman
m(CN) m(C@S) m(CS) m(MS) m(MCl) m(MS) m(MCl)
Me
4
tms 15171499 s 962 s 861 m
Me
4
tds 1498 s 978 s 848 m
Et
4
tds 1496 s 999 s 817 m
1 1528 s 964 s 882 w 384 304 388 310
2 1519 s 965 s 879 w 202 423 183 448
3 1508 s 982 s 841 w 247 229
Table 2
Chemical shifts (ppm) of the resonance signals observed in
1
H and
13
C NMR spectra of starting compounds (Me
4
tms, Me
4
tds and Et
4
tds)
and complexes 13 in DMSO-d
6
.
Compounds
1
H NMR chemical shift (ppm)
13
C NMR chemical shift (dppm)
Me
4
tms 3.383.42, d, 12H, (CH
3
of Me
4
tms) 44.63 (CH
3
, Me
4
tms)
45.31 (CH
3
, Me
4
tms)
186.98 (C@S, Me
4
tms)
Me
4
tds 3.503.59, d, 12H, (CH
3
of Me
4
tds) 42.60 (CH
3
, Me
4
tds)
47.90 (CH
3
, Me
4
tds)
192.60 (C@S, Me
4
tds)
Et
4
tds 1.161.21, t, 6H, (CH
3
of Et
4
tds) 12.01 (CH
3
, Et
4
tds)
1.361.41, t, 6H, (CH
3
of Et
4
tds) 14.12 (CH
3
, Et
4
tds)
3.943.99, q, 8H, (CH
2
of Et
4
tds) 48.08 (CH
2
, Et
4
tds)
52.36 (CH
2
, Et
4
tds)
191.69 (C@S, Et
4
tds)
1 3.352, s, 12H, (CH
3
of 1a) 44.24 (CH
3
, 1)
3.355, s, 12H, (CH
3
of 1b) 197.03 (CS
2
, 1)
2 3.30, s, 12H, (CH
3
of 2) 44.16 (CH
3
, 2)
200.82 (CS
2
, 2)
3 1.231.28, t, 12H, (CH
3
of 3) 12.95 (CH
3
, 3)
3.653.74, q, 8H, (CH
2
of 3) 48.74 (CH
2
, 3)
198.99 (CS
2
, 3)
92 I.I. Ozturk et al. / Polyhedron 67 (2014) 89103
the reaction of antimony(III) chloride with Me
4
tms in methanol
were of 1a polymorphic form (space group: P2
1
/c, a = 10.0276(5),
b = 16.4718(7), c = 8.3203(4) , a = 90.00, b = 100.598(5),
c = 90.00), while those derived from Me
4
tds in acetonitrile/
dichloromethane were of 1b form (space group: P2
1
/c,
a = 14.3425(5), b = 10.5007(3), c = 9.0543(3) , a = 90.00,
b = 97.154(3), c = 90.00). In order to assure the existence of each
polymorphic form in the bulk samples, X-ray powder diffraction
(XRPD) data were collected. The two measured patterns are clearly
different (Fig. 8) but similar to the theoretical patterns calculated
from single crystal X-ray data (Fig. S29). Both patterns show an
amorphous phase which is attributed to the holder substrate. This
is more evident for 1a due to the extremely small amount of crys-
talline powder available. Therefore, the variations in preparative
procedures lead to polymorphic forms.
The metal centers of complexes 1 (1a and 1b) and 2 with either
Sb or Bi are ve coordinated (Figs. 57). Complexes 1a, 1b and 2 are
polymers with distorted square pyramidal (SPY) geometry in each
Fig. 4.
1
H NMR spectra of 1a and 1b in DMSO-d
6
.
Table 3
Selected bond lengths () and angles () 13 complexes.
1a 1b 2
Bond length ()
Sb1Cl 2.7061(13) Sb1Cl3 2.6096(7) BiCl 2.8159(17)
Sb1S1 2.5486(13) Sb1S1 2.4665(6) BiS1 2.6834(19)
Sb1S3 2.6243(13) Sb1S11 2.5485(6) BiS2 2.7014(18)
Sb1S11 2.5098(12) Sb1S13 2.6399(7) BiS3 2.6481(18)
S1C2 1.723(5) S1C2 1.751(2) BiS4 2.937(2)
S3C2 1.717(5) S3C2 1.702(2) S1C1 1.714(7)
S11C12 1.750(5) S11C12 1.729(3) S2C1 1.744(8)
S13C12 1.676(5) S13C12 1.714(3) S3C4 1.740(8)
S4C4 1.709(8)
Bond angles ()
ClSb1S1 81.56(4) Cl3Sb1S1 85.20(2) ClBiS1 80.33(5)
ClSb1S3 150.64(4) Cl3Sb1S11 81.68(2) ClBiS2 147.38(6)
ClSb1S11 83.97(4) Cl3Sb1S13 150.23(2) ClBiS3 79.99(5)
S1Sb1S3 69.09(4) S1Sb1S11 88.34(2) ClBiS4 124.94(6)
S1Sb1S11 84.95(4) S1Sb1S13 90.36(2) S1BiS2 67.07(5)
S3Sb1S11 92.93(4) S11Sb1S13 68.75(2) S1BiS3 82.80(6)
S1BiS4 129.83(6)
S2BiS3 96.39(6)
S2BiS4 79.97(6)
S3BiS4 63.87(6)
I.I. Ozturk et al. / Polyhedron 67 (2014) 89103 93
monomeric unit. The ligand is anisobidentate l
2
-bridging in both
complexes 1 and 2. One l
2
S Sb bridging interaction in 1a forms
a highly distorted octahedral (Oh) geometry around antimony,
while two l
2
S Sb bridges in 1b leads to a pentagonal bi-pyrami-
dal (PBP) (Figs. 5 and 6). These differences in the intermolecular
interactions between 1a and 1b establish the two different poly-
morphs in the solid state (Figs. 5B and 5B). Two l
2
S Bi and
one l
2
Cl Bi bridging interaction also lead to pentagonal bipyra-
midal (PBP) geometry around bismuth ions in case of 2 (Fig. 7).
Two stronger metalsulfur bonds, with shorter MS bond
lengths (Sb1S1 = 2.5486(13) , Sb1S11 = 2.5098(12) (1a),
Sb1S1 = 2.4665(6), Sb1S11 = 2.5485(6) (1b),
BiS3 = 2.6481(18) , BiS1 = 2.6834(19) (2)) and two weaker
bond with longer MS distances (Sb1S3 = 2.6243(13), Sb1S13 =
2.924 (1a) and Sb1S3 = 2.923, Sb1S13 = 2.6399(7) (1b), Bi1
S2 = 2.7014(18) and Bi1S4 = 2.937(2) (2)) are formed. These
bonds in 1a and 1b are in the range of the corresponding SbS
lengths (varying from 2.482 to 3.009 ) found in {[SbCl
2
(-
MBZIM)
4
]
+
Cl

2H
2
O(CH
3
OH)} [15b], {[SbCl
2
(MBZIM)
4
]
+
Cl

3H
2-
O(CH
3
CN)} [15b], a,b,c-Cl-[SbCl
3
(MBZIM)
2
] [15b], a,b,d-Cl-
[SbCl
3
(EtMBZIM)
2
] [15b], a,b,c-Cl-[SbCl
3
(MTZD)
2
] [15b], and b,c,d-
Cl-[SbCl
3
(tHPMT)
2
] [15b] complexes. The equatorial angles in 1a,
1b and 2 are: ClSb1S1 = 81.56, ClSb1S13 = 124.13, S13
Sb1S3 = 79.62, S1Sb1S3 = 69.09 (1a), Cl3SbS11 = 81.68,
S11SbS13 = 68.75, S13SbS3 = 80.06, S3SbCl3 = 123.95
(1b) and ClBS1 = 80.33, S1BiS2 = 67.07, S2BiS4 = 79.97,
S4BiCl = 124.94 (2), while the corresponding basal S
axial
M
X
basal
(M = Sb or Bi and X = S or Cl) angles lie between: S11Sb
S13 = 65.09 to S11SbS3 = 92.93 (1a) S1SbS3 = 66.19 to
S1SbS13 = 90.36 (1b) and between S3BiS4 = 63.87 to S3
BiS1 = 96.39 (2), indicating high deviation from their ideal
geometry. This deviations from the 90 of the ideal SPY geometry
are due to the repulsions between the free electrons pair located
on the M (Sb or Bi) and those of the covalent MX bonds (X = S or
Cl) in accordance to the Valance Shell Electron Pair Repulsion
(VSEPR) theory.
The MCl bond distances are 2.7061(13) and 2.6096(7) in 1a
and 1b respectively and 2.8159(17) in 2. These distances are
shorter than the sum of metal and chloride van der Waals radii
(SbCl = 4.04.46 and BiCl = 4.105.57 ) [21a]. The SbCl bond
Fig. 5. (A) ORTEP diagram together with labeling scheme of two polymorphs 1a (B) Intermolecular l
2
S Sb interactions leading to polymerization of 1a.
94 I.I. Ozturk et al. / Polyhedron 67 (2014) 89103
distances are similar to those found in {[SbCl
2
(MBZIM)
4
]
+
Cl

2H
2-
O(CH
3
OH)} [15b], {[SbCl
2
(MBZIM)
4
]
+
Cl

3H
2
O(CH
3
CN)} [15b],
a,b,c-Cl-[SbCl
3
(MBZIM)
2
] [15b], a,b,d-Cl-[SbCl
3
(EtMBZIM)
2
] [15b],
a,b,c-Cl-[SbCl
3
(MTZD)
2
] [15b], and b,c,d-Cl-[SbCl
3
(tHPMT)
2
] [15b]
where the SbCl bond lengths lie between 2.376 and 3.010 . We
have previously shown that the shorter SbCl bond corresponds
to the apical chlorine, while the SbCl bond, for the terminal chlo-
rine atom in the equatorial plane, is longer than that of SbCl
apical
while the SbCl
bridging
bond distances are longer [15h]. Based on
these ndings the SbCl bonds of 1a or 1b are classied to the
SbCl
terminal
bonds.
The CS bonds varied between 1.676 and 1.751 in complexes
1a, 1b and 2; this distance is in the range of the free tetramethyl-
thiuram monosulde (1.655 ) and tetramethylthiuram disulde
(1.647 ) [21b,c]. The CS single bonds in free ligands are 1.787
1.807 for tetramethylthiuram monosulde and 1.805 for
tetramethylthiuram disulde [21b,c].
Complex 3 is dimeric (Fig. 9). Two bridging l
2
SBi bonds of
3.188(1) lead to dimeric molecular conformation in the crystal
structure. The geometry of each monomer is pentagonal bipyrami-
dal (PBP) around bismuth. The central bismuth atom is six coordi-
nated. Five sulfur atoms occupy the equatorial plane while one
sulfur atom lies in axial position. The resulting BiS
6
coordination
polyhedron approximates a pentagonal pyramid (Fig. 9).
The volumes of Hirshfeld surfaces of 13 (Fig. 10) and the cor-
responding related antimony(III) chloride compounds of formulae
{[SbCl
2
(MBZIM)
4
]Cl3H
2
O(CH
3
CN)} (MBZIM = 2-mercapto-benz-
imidazole [15b], {[SbCl
2
(MBZIM)
4
]Cl2H
2
O(CH
3
OH)} [15b],
[SbCl
3
(MBZIM)
2
] [15b], [SbCl
3
(EtMBIM)
2
] (EtMBIM = 5-ethoxy-2-
mercapto-benzimidazole) [19b], [SbCl
3
(MTZD)
2
] (MTZD = 2-mer-
capto-thiazolidine) [15b], [SbCl
3
(tHPMT)
2
], (tHPMT = 2-mercapto-
3,4,5,6-tetrahydro-pyrimidine) [15b] and [SbCl
3
(Hthcl)
2
]
n
(Hthcl = x-thiocaprolactam) [15h] are also determined and are
summarized in Table 4 among with MW and IC
50
values used for
theoretical studies.
2.5. Biological studies
The cytotoxicity of complexes 13 against human breast adeno-
carcinoma (MCF-7) and human cervix adenocarcinoma (HeLa) cells
have been evaluated by means of Trypan blue method. Table 4
summarizes the IC
50
values of 13 against HeLa and MCF-7 cells
and the corresponding ones of other related antimony(III) chloride
compounds. The IC
50
values of the two polymorphs 1a and 1b
slightly vary (Table 4). Although, both 1a and 1b possess the same
chemical composition, they affect the cell viability differently due
to the retention of the structure diversity in their solutions (see
NMR studies).
Antimony(III) and bismuth(III) complexes 13 show higher
activity than the standard anti-cancer agents; cisplatin [15e,i],
doxorubicin [11,22a] (the most active agent in advanced breast
cancer [22b]) and tamoxifen [22c] (an antiestrogen drug which
inhibits the growth of MCF-7 cells by blocking the steroid receptors
(ER-a and ER-b) [22d]) (Table 4). Compounds, 13 exhibit 2153-
fold higher activity than cisplatin against HeLa cells, while against
MCF-7 cells, 158340 fold higher activity (Table 4). Moreover, 1a
Fig. 6. (A) ORTEP diagram together with labeling scheme of two polymorphs 1b (B) Intermolecular l
2
S Sb interactions leading to polymerization of 1b.
I.I. Ozturk et al. / Polyhedron 67 (2014) 89103 95
has almost similar IC
50
value with doxorubicin against MCF-7,
while 1b, 2 and 3 are less active (0.8 to 0.4-fold) than doxorubicin
against the same cell line. Against HeLa cells, however, complexes
13 are more potent from 2 to 6 times, than doxorubicin. Com-
plexes 13 are also more effective than tamoxifen. Thus, 1a exhibit
2 times higher activity than the corresponding one of tamoxifen
against MCF-7.
Antimony(III) and bismuth(III) complexes 13 exhibit stronger
anti-proliferative activity against MCF-7 than against HeLa which
is: 23 (1a), 21 (1b), 14 (2) and 4 (3) fold higher (Table 4). Moreover,
complex 3 with higher molecular volume (MV) (Table 4, Fig. 10) is
more active against HeLa cells whereas 1a, 1b and 2 with lower MV
are more active against MCF-7. Furthermore, antimony(III) com-
plexes 1a and 1b with the non-cyclic thiocarbamates ligands (with
two sulfur donor atoms) show higher activity against HeLa cells
than the corresponding one of other related antimony(III) chloride
compounds of the heterocyclic thioamides (Table 4).
2.6. Computational studies
The physicochemical characteristics of some biologically active
compounds are related with pharmaceutical properties like bio-
availability, stability and distribution prole via the qualitative
concept of drug-likeness. The physicochemical characteristics of
some biologically active compounds are related with pharmaceuti-
cal properties like bioavailability, stability and distribution prole
via the qualitative concept of drug-likeness. There are many bio-
logically active compounds that cannot fulll the requirements
for potential drugs. These however can be valuable agents for
uncovering the hypotheses driven modeling of biological mecha-
nisms [23a]. Lipinskis Rule of Five [23b,c] is currently the gold
standard to evaluate a chemical compound as a potential drug, uti-
lizing four rules related to the calculated octanolwater partition
coefcient (clogP), the molecular mass and the hydrogen donors
and acceptors. In addition to these molecular descriptors, other
Fig. 7. (A) ORTEP diagram together with labeling scheme of 2 (B) Intermolecular l
2
S Bi and l
2
Cl Bi interactions leading to polymerization in complex 2.
96 I.I. Ozturk et al. / Polyhedron 67 (2014) 89103
researchers have also shown that molecular weight and molar
refractivity are crucial [23d] while others [23e,f] suggested that
rotatable bonds and polar surface area are related to increased oral
bioavailability. In our case, given the excellent IC
50
values of the
studied complexes, we assessed 11 conformation-dependent prop-
erties which have been successfully used (among others) as molec-
ular descriptors for drug-likeness [23g]. Most of these descriptors
are sums of structural features and only two were calculated: log
of the octanolwater partition coefcient (AlogP) using the Ghose
and Crippens method [23h] and molar refractivity (ALogP_MR).
The rest of the descriptors, used in this study, are: molecular
weight (MW), number of rotatable bonds (NRB), number of aro-
matic rings (NAR), number of rings (NR), hydrogen bond acceptors
(HBA) and hydrogen bond donors (HBD), molecular volume (MV),
surface area (SA) and polar surface area (PSA). The physicochemical
properties attributed to these descriptors contribute to the concept
of molecular property spaces [23i] which relates molecular sensi-
tivity with topological exibility. Table 5 shows the mean values
of the calculated properties for the complexes 1a, 1b, 2, 3 and for
the related antimony(III) chloride compounds.
Multivariate statistical analysis of the descriptors was carried
out with principal components analysis (PCA) using the Unscram-
bler (CAMO Software AS, Norway) software package. PCA is a sta-
tistical modeling technique which effectively removes the
redundancy of the original dataset by compressing it into a few
orthogonal uncorrelated principal components (PCs) which are
an effective indicator of the chemical diversity related to the con-
formation of each compound. 98% of the total variance was ex-
plained by the rst two PCs (the 3rd PC contributes by 1%).
Table 6 shows the eigenvectors found after the diagonalization of
the covariance matrix.
The results (Table 6) indicate high loading values from MW, MV,
SA and PSA. The rst PC, which explains 93% of the total variance,
contains particularly high loadings from MW and SA. The two
dimensional loadings plot of PC1 versus PC2 is shown in Fig. 11
(The overlapping labels in Fig. 11 are due to software limitations,
since there is not an option to manipulate the image in the multi-
variate analysis software. Nevertheless, we also believe that this is
not necessary since the overlapping labels are near zero (minimal
loadings) and therefore they have no statistical signicance in our
analysis. In contrast, the signicant high loadings values (MW, MV,
SA and PSA) are clearly labeled).
Fig. 11 describes the data structure in terms of variable correla-
tions. PSA and MV show a strong positive correlation (specic for
these ligands) while they are inversely correlated with MW. In
the analysis, compound 3 could be treated as an outlier since some
of its specic molecular descriptors are vastly different compared
to the others. However, no signicant discrepancy is found regard-
ing the nal PC loadings.
The correlation loadings plot indicates that all variables are
highly correlated; therefore the distinct signicance of each vari-
able may not be apparent (especially with our small dataset). To
relate the variation of the IC
50
values for HeLa cells (dependent var-
iable) to the variations of the molecular descriptors (independent
variables) statistically indexed by PCA, we have carried out partial
least squares (PLS) regression analysis which performs well when
the x-data are correlated like in this case. The PLS regression model
with 3 latent components constructed from the set of the descrip-
tors with high PC loadings was not satisfactory due to the low Pear-
son correlated coefcient (R
2
= 0.5). However, a similar regression
model predicting the activity of these compounds was successfully
Fig. 8. The two clearly different XRPD patterns of 1a and 1b measured.
Fig. 9. Molecular formula of complex 3.
I.I. Ozturk et al. / Polyhedron 67 (2014) 89103 97
constructed from the following descriptors: MW, PSA, SA, MV,
AlogP_MR, HBA and HBD where the latter was considered as highly
signicant followed by PSA and described by the equation:
IC
50
(HeLa)
= 0.02 ALogP_MR + 0.002 MW 0.74 HBA + 1.23
HBD + 0.01 MV + 0.003 SA 0.04 PSA + 2.2. Fig. 12 depicts the
graphical representation of the linear model and the corresponding
tting parameters.
Our statistical analysis concentrated on important molecular
descriptors closely related to the comparable geometric parame-
ters of the two polymorphs. Therefore, we have particularly
emphasized to structural terms although energetic terms, solva-
tion effects and toxicity studies are crucial evaluation parameters.
2.7. Docking studies
To clarify the possible involvement of estrogen receptors (ERs)
which are present in MCF-7 cells [14a] in the mechanism of action
of 1a, 1b and 2 in contrast to 3 (Table 4) molecular docking studies
were performed. Estrogen receptors (ER) are of two forms, alpha
(a) and beta (b) and play a crucial role in mammary gland develop-
ment and morphogenesis [24a]. The crystal structure of estrogen
receptor a (ERa) complexed with 17b-estradiol (1A52) [24b] was
obtained from Protein Data Bank (PDB). Estradiol is a natural estro-
gen which can bind in ERs [24a]. Complexes 1a, 1b, 2 and 3 were
examined regarding their ability to be docked into the ligand bind-
ing domains. Validation docking was performed and the root mean
square deviation (RMSD) between the co-crystallized and the
docked ligand and was found 0.59 (Fig. 13A).
Both 1a and 1b compounds were docked into the ligand binding
domains specied by the two larger cavities of volume 142 and
133
3
(Fig. 13B). They also adopt the same conformation having
slightly different interaction energies of 83.5 and 84.7 (in scor-
ing arbitrary units) respectively with the receptor which probably
explains their similar activity. The corresponding ligandprotein
Fig. 10. Hirshfeld surfaces of 1 (A), 2 (B) and 3 (C).
98 I.I. Ozturk et al. / Polyhedron 67 (2014) 89103
Table 4
Hirshfeld surfaces Volumes, Molecular weights and IC
50
against MCF-7 and HeLa cell lines of 13 and the corresponding ones of other related antimony(III) chloride compounds.
Compound Volume (
3
) MW (gr/mol) IC
50
(lM) Refs.
HeLa MCF-7
1a 330.6 397.61 0.46 0.07 0.020 0.003
1b 331.19 397.61 0.51 0.10 0.024 0.004
2 414.73 484.84 0.33 0.03 0.023 0.003
3 1207.07 1307.47 0.19 0.02 0.043 0.008
{[SbCl
2
(MBZIM)
4
] Cl 3H
2
O(CH
3
CN)} 754.26 911.94 6.4 1.6 [15b]
{[SbCl
2
(MBZIM)
4
] Cl 2H
2
O(CH
3
OH)} 739.79 896.93 7.0 2.0 [15b]
[SbCl
3
(MBZIM)
2
] 460.02 528.49 7.7 1.2 [15b]
[SbCl
3
(EtMBIM)
2
] 572.77 616.58 6.9 1.1 [15b]
[SbCl
3
(MTZD)
2
] 360.9 466.50 6.8 4.4 [15b]
[SbCl
3
(tHPMT)
2
] 418.77 460.49 7.7 2.5 [15b]
[SbCl
3
(Hthcl)
2
]
n
471.6 484.51 12.23 2.27 [15h]
Cisplatin 10 6.81 0.32 [15e,i]
Doxorubicin 1.12 0.018 [11,22a]
Tamoxifen 0.0455 [22c]
*
This work, MBZIM = 2-mercapto-benzimidazole, EtMBIM = 5-ethoxy-2-mercapto-benzimidazole, MTZD = 2-mercapto-thiazolidine, tHPMT = 2-mercapto-3,4,5,6-tetrahy-
dro-pyrimidine, Hthcl = x-thiocaprolactam.
Table 5
Molecular descriptors mean values.
Property Mean value
AlogP 4.78
ALogP_MR 124.2
MW 632.1
NRB 6
NR 4
NAR 1
HBA 8
HBD 4
MV 500.8
SA 453.8
PSA 185.6
Table 6
Normalized X- loadings for the rst two PCs.
PC1 PC2
ALogP 7.826e-03 3.237e-02
ALogP_MR 0.168 9.962e-03
MW 0.730 0.487
NRT 1.039e-02 1.959e-02
NR 6.522e-03 9.310e-03
NAR 2.237e-03 1.412e-02
HBA 1.239e-02 9.499e-03
HBD 6.147e-03 3.312e-02
MV 0.363 0.726
SA 0.501 4.142e-02
PSA 0.237 0.481
Fig. 11. X-Loadings plot (x-expl: 93%, 5%).
Fig. 12. Pls regression analysis for the activity against HeLa cells.
I.I. Ozturk et al. / Polyhedron 67 (2014) 89103 99
interaction in the case of estradiol was found 113.8 while this li-
gand was further stabilized by hydrogen bonding interactions. In
the case of 1a and 1b the complexes are stabilized in the hydro-
phobic core by van der Waals interactions. Hydrophobic van der
Waals contacts are also responsible for the docking of 2 into the
same pocket with almost the same interaction energy with 1a
and 1b (78.3). 3, due to its bulk dimensions, cannot reach the
binding sites and therefore interacts with the residues present at
the receptors surface exhibiting hydrogen bonding interaction
with the N atom of Leu462.
Tamoxifen is a well-known breast cancer drug which acts as an
estrogen antagonist inhibiting the growth of tumours dependent
on estrogen stimulation. The crystal structure (PDB ID: 3ERT) of
the ERa complex with 4-hydroxytamoxifen (an active metabolite
of tamoxifen) shows that ligand binding causes a conformational
shift of helix 12 into an adjacent coactivator site and shows a
remarkable resemblance with docking results with 1A52 of 1a
and 1b complexes regarding their binding conformation (Fig. 14).
Although the two structures (complex versus 4-hydroxytamoxifen)
present critical differences (hydroxyl groups, phenyl rings, size)
they adopt similar conformation. The dimethyl-amino-ethyl side-
chain extends to the space also available for the thiuram moiety
while the phenyl ring moves deeper into the binding pocket like
the Cl atom of 1a and 1b. Complexes 1a and 1b show signicant
hydrophobic interactions into the binding pocket while of 4-
hydroxytamoxifen also exhibits signicant hydrogen bonding
interactions with Glu353, Thr347, Phe404 and Arg394. The similar
binding is probably indicative of a similar action mechanism to-
wards ERs and it might be explain the same IC
50
values between
tamoxifen and 1a.
Fig. 13. (A) Validation docking results of 1A52 with 17b-estradiol. Drawn with LIGOPLOT+ [24c]. (B) The ERa binding pocket with 1a and 1b.
100 I.I. Ozturk et al. / Polyhedron 67 (2014) 89103
3. Conclusions
Three antimony(III) or bismuth(III) chloride complexes of for-
mulae {[SbCl(Me
2
DTC)
2
]
n
} (1), {[BiCl(Me
2
DTC)
2
]
n
} (2) and {[Bi(Et
2-
DTC)
3
]
2
} (3) were synthesized. Alterations in preparation of 1 by
the use of different processor reagents (Me
4
tms instead of Me
4
tds)
and solvation effect (Scheme 1), lead to different polymorphic
forms in the solid state (1a and 1b).
The cytotoxicity of complexes 13 against human cervix adeno-
carcinoma (HeLa) and human breast adenocarcinoma (MCF-7) cells
have been evaluated. Although both 1a and 1b possess the same
chemical composition, the IC
50
values of the two polymorphs 1a
and 1b varies slightly (Table 4). Furthermore, antimony(III) com-
plexes 1a and 1b with thiocarbamates exhibit higher activity
against HeLa cells than that of other related antimony(III) chloride
compounds of the heterocyclic thioamide (Table 4). Complex 3
occupied the higher molecular volume (MV) (Table 4, Fig. 10)
and is more active against HeLa cells, while 1a, 1b and 2 with lower
MV are more active against MCF-7.
Complexes 13 show higher activity against MCF-7 than HeLa
(Table 4). Tiekink et.al, have shown that bismuth dithiocarbamate
complexes of general formula Bi(S
2
CNR
2
)
3
demonstrate potent
activity against breast cancer (MCF-7, estrogen receptor (ER)+/pro-
gesterone receptor (PgR)+) in contrast to breast cancer (EVSA-T),
estrogen receptor (ER)/progesterone receptor (PgR)) cells [11].
The higher activity of these complexes (Bi(S
2
CNR
2
)
3
) against
MCF-7 reveals the involvement of estrogen receptors (ERs) in their
mechanism of cytostasis together with progesterone receptors
(PgR) [progesterone is a precursor for the major steroid hormones
(androgens, estrogens, corticosteroids) which adjust ERs concen-
trations among with estradiol [25]]. These ndings support our
hypothesis for the involvement of ERs in the mechanism of cytos-
tasis of 1a, 1b and 2. However, the higher activity of 13 observed
against MCF-7 than HeLa cells may be also due to the different tis-
sues origin (breast or cervix). Molecular docking studies have
shown that 1a, 1b and 2 are docked in the same pocket with the
ERs modulators (like 17b-estradiol, a natural estrogen [24a]).
Tamoxifen, a known anti-estrogen drug, on the other hand, which
inhibits the growth of MCF-7 cells by blocking the steroid receptors
(ER-a and ER-b) [22d], is also docked in the same pocket as 1a, 1b
and 2 (Fig. S28). This might be due to the same mechanism of
cytostasis towards MCF-7 cells adopted either by 1a, 1b and 2 or
tamoxifen. 3 cannot reach this binding site due to its bulk dimen-
sions. This inability to enter the binding sites is compatible with its
reduced activity against MFC-7 cells in regards to 1a, 1b and 2.
Multivariate analysis studies of 11 conformation-dependent
molecular descriptors have shown (Table 6) high loading values
from molecular weight (MW), molecular volume (MV), surface
area (SA) and polar surface area (PSA). Molecular docking studies
explained the experimental IC
50
values in terms of the known li-
gand binding domains of ER (1A52) while PLS analysis with only
three latent components constructed a linear theoretical model
which effectively predicts the experimental inhibitory activity of
the studied complexes.
4. Experimental
4.1. Materials and instruments
All solvents used were of reagent grade; antimony(III) chloride
(Aldrich), bismuth(III) chloride (Aldrich), tetramethylthiuram
monosulde (Aldrich), tetramethylthiuram disulde (Aldrich) and
tetraethylthiuramdisulde (Aldrich) were used with no other puri-
cation. Elemental analyses for C, H, N, and S were carried out with
a Carlo Erba EA MODEL 1108 elemental analyzer. Melting points
were measured in open tubes with a STUART-SMP10 scientic
apparatus and are uncorrected. IR spectra from 4000 to 370 cm
1
were obtained in KBr pellets while far-IR spectra (40050 cm
1
)
were obtained in polyethylene discs with a Perkin-Elmer Spectrum
GX FT-IR spectrometer. The FT-Raman spectra were recorded with
a Bruker IFS 66 spectrometer with an FRA 106 Raman module
attachment and Nd
3+
/YAG laser excitation at 1064 nm.
1
H and
13
C NMR spectra were recorded with a Bruker AC250 MHz FT
NMR and Bruker Avance AV-500 MHz LC NMR instruments in
DMSO-d
6
with chemical shifts given in parts per million referenced
to internal TMS (H). Thermal studies were carried out on a Shima-
dzu DTG-60 simultaneous and Thermal GravimetryDifferential
Thermal Analysis (TGDTA) apparatus for complexes 1, 2 and a
Seteram Labsys TG-DTA for 3 under N
2
ow (50 cm
3
min
1
) with
a heating rate of 10 C min
1
. X-ray powder diffraction patterns,
from the powder derived from crystals, were obtained using a Bru-
ker AXS D8 Advance diffractometer in BraggBrentano geometry
equipped with a Cu sealed-tube radiation source (k = 1.54178 )
and a secondary beam graphite monochromator.
4.2. Synthesis and crystallization of {[SbCl(Me
2
DTC)
2
]
n
} (1),
{[BiCl(Me
2
DTC)
2
]
n
} (2) and {[Bi(Et
2
DTC)
3
]
2
} (3)
4.2.1. {[SbCl(Me
2
DTC)
2
]
n
} (1)
A solution of tetramethylthiuram monosulde (0.25 mmol,
0.052 g) in methanol (1a) or tetramethylthiuram disulde
(0.25 mmol, 0.060 g) in acetonitrile (1b) (10 mL) was added to a
solution of SbCl
3
(0.25 mmol, 0.057 g) in methanol (1a) or dichlo-
romethane solution (1b) 10 mL, under stirring for 30 min. After-
wards, the solutions were ltered off. The clear yellow solutions
were kept in darkness at room temperature to give light yellow
crystals.
4.2.2. {[BiCl(Me
2
DTC)
2
]
n
} (2)
A solution of BiCl
3
(0.25 mmol, 0.079 g) in methanol (10 ml)
was added to an acetonitirile solution (10 mL) of 0 tetramethyl-
thiuram monosulde (.25 mmol, 0.052 g) or tetramethylthiuram
disulde (0.25 mmol, 0.060 g) under stirring for 30 min. After-
wards, the solutions were ltered off. The resulting clear yellow
solutions were kept in darkness at room temperature to give yel-
low crystals.
Fig. 14. Docking results of 1A52 with 4-hydroxytamoxifen (a known anti-estrogen
drug) vs. 1a complex.
I.I. Ozturk et al. / Polyhedron 67 (2014) 89103 101
4.2.3. {[Bi(Et
2
DTC)
3
]
2
} (3)
0.25 mmol bismuth(III) chloride (0.079 g) were dissolved in
methanol (10 ml) and the resulting solution is added to a methanol
solution (10 mL) of tetraethylthiuram disulde (0.25 mmol,
0.074 g). The solution was stirred 30 min and then was ltered
off. The clear light yellow solution was kept in darkness at room
temperature to give yellow crystals.
1: Light yellow crystals, yield: 70% (method A), 75% (method B),
melting point: 224226 C. Elemental Anal. Calc. for C
6
H
12
ClN
2
S
4-
Sb: C, 18.12; H, 3.04; N, 7.04; S, 32.25. Found: C, 18.17; H, 3.09;
N, 7.12; S, 32.33%. IR (cm
1
): 2927w, 1524s, 1383s, 1241s, 1148s,
1043 m, 1016w, 972s, 830w, 570m, 444m, 385w, 374m.
2: Yellow crystals, yield 80% (method A), yield 73% (method B),
melting point: >300 C. Elemental Anal. Calc. for C
6
H
12
ClN
2
S
4
Bi: C,
14.86; H, 2.49; N, 5.78; S, 26.45. Found: C, 14.90; H, 2.53; N, 5.82; S,
26.54%. IR (cm
1
): 2925w, 1520s, 1383s, 1240s, 1147s, 1042m,
965s, 568m, 445m.
3: Yellow crystal, yield 75%, melting point: 133135 C. Elemen-
tal Anal. Calc. for C
15
H
30
N
3
S
6
Bi: C, 27.56; H, 4.63; N, 6.43; S, 29.43.
Found: C, 27.63; H, 4.70; N, 6.38; S, 29.52: IR (cm
1
): 2974w,
2931w, 1506s, 1457w, 1432s, 1378w, 1354m, 1297w, 1273s,
1200m, 1147m, 1093w, 1075m, 982m, 908m, 841m, 778w,
561w, 375w.
4.3. X-ray structure determination
Intensity data for 1a and 1b were collected on a KUMA KM4CCD
four-circle diffractometer [26a] with a CCD detector, using graphite
monochromated Mo Ka radiation (k = 0.71073 ). Cell parameters
were determined by a least squares t [26b]. All data were cor-
rected for Lorentz-polarization effects and absorption [26b]. The
structures were solved with direct methods with SHELXS97 [26c]
and rened by full-matrix least squares procedures on F
2
with SHEL-
XL97 [26d].
Intensity data for the crystals of 23 were collected on an Ox-
ford Diffraction CCD instrument, using graphite monochromated
Mo radiation (k = 0.71073 ). Cell parameters were determined
by least-squares renement of the diffraction data from 25 reec-
tions [26b]. All data were corrected for Lorentz-polarization effects
and absorption [26b,e]. The structures were solved with direct
methods with SHELXS97 [26c] and rened by full-matrix least-
squares procedures on F
2
with SHELXL97 [26d]. All non-hydrogen
atoms were rened anisotropically, hydrogen atoms were located
at calculated positions and rened via the riding model with iso-
tropic thermal parameters xed at 1.2 (1.3 for CH
3
groups) times
the Ueq value of the appropriate carrier atom.
The molecular volumes dened as the areas in the crystal
where the electron density which originates from a given molecule
is higher than the density from the rest of the crystal (the surface
limiting this space is called Hirshfeld surface [26f]) were calcu-
lated with the CrystalExplorer program [26g].
Signicant crystallographic data for antimony(III) chloride and
bismuth(III) chloride complexes:
1a: C
6
H
12
ClN
2
S
4
Sb: MW = 397.61, monoclinic, P2
1
/c,
a = 10.0276(5), b = 16.4718(7), c = 8.3203(4) , b = 100.598(5),
V = 1350.84(11)
3
, Z = 4, D
calc
= 1.955 g cm
3
, l = 2.8 mm
1
,
reections collected: 5741, independent: 2805, R
int
= 0.030. Final
R indices [I > 2r(I)]; R
1
= 0.0385, wR
2
= 0.0776, S = 1.06.
1b: C
6
H
12
ClN
2
S
4
Sb: MW = 397.61, monoclinic, P2
1
/c,
a = 14.3425(5), b = 10.5007(3), c = 9.0543(3) , b = 97.154(3),
V = 1353.02(8)
3
, Z = 4, D
calc
= 1.952 g cm
3
, l = 2.8 mm
1
, reec-
tions collected: 25233, independent: 2833, R
int
= 0.032, Final R
indices [I > 2r(I)]; R
1
= 0.0213, wR
2
= 0.0564, S = 1.11.
2: C
6
H
12
ClN
2
S
4
Bi: MW = 484.84, monoclinic, P2
1
/c,
a = 10.0523(3), b = 16.1457(6), c = 8.1648(3) , b = 99.668(3),
V = 1306.34(8)
3
, Z = 4, D
calc
= 2.465 g cm
3
, l = 14.3 mm
1
,
reections collected: 5026, independent: 2297, R
int
= 0.035, Final
R indices [I > 2r(I)]; R
1
= 0.0333, wR
2
= 0.0657, S = 1.17.
3: (C
15
H
30
N
3
S
6
Bi)
2
: MW = 1307.47, monoclinic, P2
1
/c, a =
12.3965(8), b = 13.5006(8), c = 14.7833(9) , b = 99.942(6), V =
2437.0(3)
3
, Z = 4, D
calc
= 1.782 g cm
3
, l = 7.8 mm
1
, reections
collected: 9390, independent: 4290, R
int
= 0.057, Final R indices
[I > 2r(I)]; R
1
= 0.0431, wR
2
= 0.1081, S = 1.03.
4.4. Biological tests
Cell viability was determined as previously described [15h].
Biological experiments were carried in dimethyl sulfoxide in Dul-
beccos Modied Eagles Medium solutions (DMEM)DMSO/DMEM
(0.000050.0055% v/v) for the complexes 13. In case of 1a and
1b, the DMSO/DMEM solutions were 0.000050.006% v/v. Stock
solutions of the complexes 13, (0.01 M) in DMSO were freshly
prepared and diluted in with cell culture medium to the desired
concentration (0.0050.800 lM). The low concentration of the
complexes used for the cells screening tests allow the formation
of clear solution. MCF-7 and HeLa cells were seeded onto 24-well
plates at a density of 3 10
4
cells per well, respectively, and incu-
bated for 24 h before the experiment. Results are expressed in
terms of IC
50
values, which is the concentration of drug required
to inhibit cell growth by 50% compared to control, after of 48 h
incubation of the complexes towards cell lines.
4.5. Computational studies
We have performed in silico and molecular docking studies
according to Refs. [14a,14d].
Acknowledgements
The NMR spectra of compounds 1a and 1b were recorded by Dr
C.G. Tsiafoulis, who is acknowledged. The NMR Centre of the Net-
work of Research Supporting Laboratories of the University of
Ioannina and the Greek Community Support Framework III, Regio-
nal Operational Program of Epirus 20002006 (MIS 91629), for
supporting the purchase of an LC-NMR cryo instrument are also
acknowledged. This research was carried out in partial fulllment
of the requirements for the master thesis of Mrs C.N.B. under the
supervision of S.K.H. within the graduate program in Bioinorganic
Chemistry. The research of I.I.O was supported by the Namik Kemal
University Scientic Research Projects Fund (Project No.
NKUBAP.00.10.AR.10.1).
Appendix A. Supplementary data
CCDC 909398, 909399, 910135, and 910136 contain the supple-
mentary crystallographic data for compounds 1a, 1b, 2 and 3,
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 Centre, 12 Union Road, Cambridge CB2 1EZ,
UK; fax: (+44) 1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.poly.2013.08.052.
References
[1] G.D. Thorn, R. Ludwig, The Dithiocarbamates and Related Compounds, Elsevier,
Amsterdam, 1981.
[2] E.J. Buttereld, D.C. Torgeson, Fungicides, in: H.F. Mark, D.F. Othmer, C.G.
Overberger, G.T. Seaborg (Eds.), Kirk-Ortmer Encyclopedia of Chemical
Technology, Wiley, New York, 1991.
[3] T. Kitson, Educ. Chem. (1985) 43.
[4] P.K. Gessner, T. Gessner, Disulram and its Metabolite, Diethydithiocarbamate,
Chapman and Hall, London, 1992.
102 I.I. Ozturk et al. / Polyhedron 67 (2014) 89103
[5] Y. Tatara, Y.C. Lin, Y. Bamba, T. Mori, T. Uchida, Biochem. Biophys. Res.
Commun. 384 (2009) 394.
[6] L.I. Viktoriano, Coord. Chem. Rev. 196 (2000) 383.
[7] J.A. McCleverty, N. Morrison, J. Chem. Soc., Dalton Trans. 21 (1976) 2169.
[8] (a) B.A. Prakasam, K. Ramalingam, G. Bocelli, A. Cantoni, Phosphorus Sulfur
184 (2009) 2020;
(b) L.I. Victoriano, Polyhedron 19 (2000) 2269.
[9] (a) P.T. Beurskens, W.P. Bosman, J.A. Cras, J. Cryst. Mol. Struct. 2 (1972) 183;
(b) J. Willemse, J.J. Steggerda, Chem. Commun. (1969) 1123.
[10] (a) H. Abrahamson, J.R. Heiman, L.H. Pignolet, Inorg. Chem. 14 (1975) 2070;
(b) P.J.H.A.M. van de Leemput, J.A. Cras, J. Willemse, Rec. Trav. Chim. Pays Bas
96 (1977) 78;
(c) E.R.T. Tiekink, X.F. Yan, C.G. Young, Aust. J. Chem. 45 (1992) 897;
(d) R.N. Jowitt, P.C.H. Mitchell, Inorg. Nucl. Chem. Lett. 4 (1968) 39;
(e) Z.B. Varadi, A. Nieuwpoort, Inorg. Nucl. Chem. Lett. 10 (1974) 801;
(f) A. Nieuwpoort, H.M. Claessen, J.G.M. van de Linden, Inorg. Nucl. Chem. Lett.
11 (1975) 869.
[11] H. Li, C.S. Lai, J. Wu, P.C. Ho, Di. de Vos, E.R.T. Tiekink, J. Inorg. Biochem. 101
(2007) 809.
[12] (a) R.-Z. Sun, Y.-C. Guo, W.-M. Liu, Chin. J. Struct. Chem. 31 (2012) 655;
(b) H.P.S. Chauhan, A. Bakshi, S. Bhatiya, Spectrochim. Acta Part A Mol. Biomol.
Spectrosc. 81 (2011) 417;
(c) H.P.S. Chauhan, A. Bakshi, S. Bhatiya, Sulfur, and Silicon and the Related
Elements 186 (2011) 345;
(d) C.L. Teske, W. Bensch, Z. Anorg. Allg. Chem. 637 (2011) 406;
(e) H.P.S. Chauhan, Appl. Organomet. Chem. 24 (2010) 317;
(f) H.P.S. Chauhan, U.P. Singh, Appl. Organomet. Chem. 21 (2007) 880;
(g) H. Yin, F. Li, D. Wang, J. Coord. Chem. 60 (2007) 1133.
[13] (a) H.P.S. Chauhan, N.M. Shaik, U.P. Singh, Appl. Organomet. Chem. 20 (2006)
142;
(b) H.P.S. Chauhan, U.P. Singh, Appl. Organomet. Chem. 20 (2006) 404;
(c) H.P.S. Chauhan, K. Kori, N.-M. Shaik, S. Mathur, V. Huch, Polyhedron 24
(2005) 89;
(d) Y. Liu, E.R.T. Tiekink, Appl. Organomet. Chem. 18 (2004) 299;
(e) H.-D. Yin, C.-H. Wang, Appl. Organometal. Chem. 18 (2004) 420;
(f) H.-D. Yin, C.-H. Wang, Wang, Appl. Organomet. Chem. 18 (2004) 199;
(g) C.S. Lai, E.R.T. Tiekink, Appl. Organomet. Chem. 17 (2003) 195;
(h) S.S. Garje, V.K. Jain, Coord. Chem. Rev. 236 (2003) 35;
(i) I. Baba, S. Ibrahim, Y. Farina, A.H. Othman, I.A. Razak, H.-K. Fun, S.W. Ng,
Acta Crystallogr., Sect. E 57 (2001) m39;
(j) V. Venkatachalam, K. Ramalingam, G. Bocelli, A. Cantoni, Inorg. Chim. Acta
261 (1997) 23.
[14] (a) D.B. Shpakovsky, C.N. Banti, G. Beaulieu-Houle, N. Kourkoumelis, M.
Manoli, M.J. Manos, A.J. Tasiopoulos, S.K. Hadjikakou, E.R. Milaeva, K.
Charalabopoulos, T. Bakas, I.S. Butlerd, N. Hadjiliadis, Dalton Trans. 41
(2012) 14568;
(b) S. Sommer, S.A.W. Fuqua, Semin. Cancer Biol. 11 (2001) 339;
(c) P. Bulzomi, P. Galluzzo, A. Bolli, S. Leone, F. Acconcia, M. Marino, J. Cell.
Physiol. 227 (2012) 1891;
(d) V.I. Balas, C.N. Banti, N. Kourkoumelis, S.K. Hadjikakou, G.D. Geromichalos,
D. Sahpazidou, L. Male, M.B. Hursthouse, B. Bednarz, M. Kubicki, K.
Charalabopoulos, N. Hadjiliadis, Aust. J. Chem. 65 (2012) 1625.
[15] (a) S.K. Hadjikakou, C.D. Antoniadis, N. Hadjiliadis, M. Kubicki, J. Binolis, S.
Karkabounas, K. Charalabopoulos, Inorg. Chim. Acta 358 (2005) 2861;
(b) I.I. Ozturk, S.K. Hadjikakou, N. Hadjiliadis, N. Kourkoumelis, M. Kubicki, M.
Baril, I.S. Butler, J. Balzarini, Inorg. Chem. 46 (2007) 8652;
(c) I.I. Ozturk, S.K. Hadjikakou, N. Hadjiliadis, N. Kourkoumelis, M. Kubicki, A.J.
Tasiopoulos, H. Scleiman, M.M. Barsan, I.S. Butler, Inorg. Chem. 48 (2009)
2233;
(d) S.K. Hadjikakou, I.I. Ozturk, M.N. Xanthopoulou, P.C. Zachariadis, S.
Zartilas, S. Karkabounas, N. Hadjiliadis, J. Inorg. Biochem. 102 (2008) 1007;
(e) I.I. Ozturk, S. Filimonova, S.K. Hadjikakou, N. Kourkoumelis, V. Dokorou,
M.J. Manos, A.J. Tasiopoulos, M.M. Barsan, I.S. Butler, E.R. Milaeva, J. Balzarini,
N. Hadjiliadis, Inorg. Chem. 49 (2010) 488;
(f) I.I. Ozturk, A.K. Metsios, S. Filimonova-Orlova, N. Kourkoumelis, S.K.
Hadjikakou, E. Manos, A.J. Tasiopoulos, S. Karkabounas, E.R. Milaeva, N.
Hadjiliadis, Med. Chem. Res. 21 (2012) 3523;
(g) I.I. Ozturk, N. Kourkoumelis, S.K. Hadjikakou, M.J. Manos, A.J. Tasiopoulos,
I.S. Butler, J. Balzarini, N. Hadjiliadis, J. Coord. Chem. 64 (2011) 3859;
(h) I.I. Ozturk, C.N. Banti, M.J. Manos, A.J. Tasiopoulos, N. Kourkoumelis, K.
Charalabopoulos, S.K. Hadjikakou, J. Inorg. Biochem. 109 (2012) 57;
(i) I.I. Ozturk, O.S. Urgut, C.N. Banti, N. Kourkoumelis, A.M. Owczarzak, M.
Kubicki, K. Charalabopoulos, S.K. Hadjikakou, Polyhedron 52 (2013) 1403.
[16] (a) J.A. Howard, D.R. Russell, W. Scutcher, Acta Crystallogr., Sect. A 31 (1975)
S141;
(b) C.L. Raston, A.H. White, J. Chem. Soc., Dalton Trans. (1976) 791;
(c) H.-D. Yin, M. Hong, C.-H. Wang, Indian J. Chem., Sect A 44 (2005) 1401;
(d) Chian Sing Lai, E.R.T. Tiekink CCDC Private, Communication, 2008.
[17] H.P.S. Chauhan, U.P. Singh, Appl. Organomet. Chem. 20 (2006) 404.
[18] (a) M.M. Coleman, J.L. Koenig, J.R. Shelton, J. Polym. Sci. 12 (1974) 1001;
(b) M.M. Milosavljevic, A.D. Morinkovic, J.M. Morkovic, D.V. Brkovic, M.M.
Milosavljevic, Chem Ind Chem Eng Q 18 (2012) 73.
[19] (a) Y. Marqueton, A. Miniewicz, R. Jakubas, Ferroelectrics 145 (1993) 109;
(b) M.G.B. Drew, J.M. Kisenyi, G.R. Willey, S.O. Wandiga, J. Chem. Soc., Dalton
Trans. (1984) 1717.
[20] (a) F. Zouari, A.B. Salah, Phase Transitions: A Multinational Journal 78 (2005)
317;
(b) S.R. Luan, Y.H. Zhu, Y.Q. Jia, Q. Cao, J. Therm. Anal. Calorim. 99 (2010) 523.
[21] (a) S.S. Batsanov, Inorg. Mater 37 (2001) 871. translated from; Neorg. Mater.
2001, 37, 10311046;
(b) Y. Wang, J.H. Liao, C.H. Ueng, Acta Crystallogr., Sect. C 42 (1986) 1420;
(c) M. Colapietro, A. Domenicano, A. Vaciago, Acta Crystallogr., Sect. B 32
(1976) 2581.
[22] (a) D.Y. Lu, M. Huang, C.H. Xu, W.Y. Yang, C.X. Hu, L.P. Lin, L.J. Tong, M.H. Li, W.
Lu, X.W. Zhang, J. Ding, BMC Pharmacology 5 (2005) 11;
(b) R. Paridaens, L. Biganzoli, P. Bruning, J.G.M. Klijn, T. Gamucci, S. Houston, R.
Coleman, J. Schachter, A. Van Vreckem, R. Sylvester, A. Awada, J. Wildiers, M.
Piccart, J. Clin. Oncol. 18 (2000) 724;
(c) J. Hoffmann, R. Bohlmann, N. Heinrich, H. Hofmeister, J. Kroll, H. Kunzer,
R.B. Lichtner, Y. Nishino, K. Parczyk, G. Sauer, H. Gieschen, H.F. Ulbrich, M.R.
Schneider, J. Natl Cancer Inst. 96 (2004) 210;
(d) A.S. Levenson, V.C. Jordan, Cancer Res. 57 (1997) 3071.
[23] (a) C. Lipinski, A. Hopkins, Nature 432 (2004) 855;
(b) C.A. Lipinski, F. Lombardo, B.W. Dominy, P.J. Feeney, Adv. Drug Delivery
Rev. 46 (2001) 3;
(c) C.A. Lipinski, F. Lombardo, B.W. Dominy, P.J. Feeney, Adv. Drug Delivery
Rev. 23 (1997) 3;
(d) A.K. Ghose, V.N. Viswanadhan, J.J. Wendoloski, J. Comb. Chem. 1 (1999) 55;
(e) D.F. Veber, S.R. Johnson, H.Y. Cheng, B.R. Smith, K.W. Ward, K.D. Kopple, J.
Med. Chem. 45 (2002) 2615;
(f) D.E. Clark, S.D. Pickett, Drug Discov. Today 5 (2000) 49;
(g) M. Feher, J.M. Schmidt, J. Chem. Inf. Comp. Sci. 43 (2003) 218;
(h) A.K. Ghose, G. Crippen, J. Comp. Chem. 7 (1986) 565;
(i) G. Vistoli, A. Pedretti, B. Testa, Drug Discov. Today 13 (2008) 285.
[24] (a) V.V. Sumbayev, E.C. Bonefeld-Jrgensen, T. Wind, P.A. Andreasen, FEBS
Lett. 579 (2005) 541;
(b) D.M. Tanenbaum, Y. Wang, S.P. Williams, P.B. Sigler, Proc. Natl. Acad. Sci.
U.S.A. 95 (1998) 5998;
(c) R.A. Laskowski, M.B. Swindells, J. Chem. Inf. Model. 51 (2011) 2778.
[25] J.P. Wiebe, Endocr-Relat Cancer 13 (2006) 717.
[26] (a) CRYSALIS CCD, Version 1.171.31.5 (release 28-08-2006 CrysAlis 171.NET),
Oxford Diffraction, Ltd.;
(b) CRYSALIS RED, Version 1.171.31.5 (release 2808-2006 CrysAlis 171.NET);
Oxford Diffraction, Ltd.;
(c) G.M. Sheldrick, Acta Crystallogr., Sect. A 46 (1990) 467;
(d) G.M. Sheldrick, SHELXL-97, Program for the Renement of Crystal
Structures; University of Gttingen, Gttingen, Germany, 1997;
(e) Oxford Diffraction, CRYSALIS CCD and CRYSALIS RED, Version p171.29.2, Oxford
Diffraction Ltd., Abingdon, Oxford, England, 2006.;
(f) M.A. Spackman, D. Jayatilaka, CrystEngComm 11 (2009) 19;
(g) CRYSTALEXPLORER (Version 3.0), S.K. Wolff, D.J. Grimwood, J.J. McKinnon, M.J.
Turner, D. Jayatilaka, M.A. Spackman, University of Western Australia, 2012.
I.I. Ozturk et al. / Polyhedron 67 (2014) 89103 103