Synthesis, structural characterization, and evaluation of biological activity of organotin(IV) complexes with 2-hydroxy-5-methoxybenzaldehyde-N(4)-methylthiosemicarbazone

Article abstract of DOI:10.1016/j.jorganchem.2016.04.007

The reaction of organotin(IV) chloride(s) with 2-hydroxy-5-methoxybenzaldehyde-N(4)-methylthiosemicarbazone [H₂dmmt, (1)] in the presence of potassium hydroxide yielded four new stable complexes, namely, [MeSnCl(dmmt)] (2), [BuSnCl(dmmt)] (3),

Full text of DOI:10.1016/j.jorganchem.2016.04.007

Journal of Organometallic Chemistry 813 (2016) 71e77
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis, structural characterization, and evaluation of biological
activity of organotin(IV) complexes with 2-hydroxy-5-
methoxybenzaldehyde-N(4)-methylthiosemicarbazone
a
,
*
b
c
c
M.A. Salam , Mouayed A. Hussein , Irmawati Ramli , Md. Saiful Islam
a
Bangladesh Petroleum Exploration and Production Co. Ltd. (BAPEX), 4 Karwan Bazar, BAPEX Bhabon, Dhaka 1215, Bangladesh
Department of Chemistry, College of Science, University of Basrah, Basra 61004, Iraq
Department of Chemistry, Faculty of Science, University Putra Malaysia, UPM Serdang, 43400 Selangor, Malaysia
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 December 2015
Received in revised form
The reaction of organotin(IV) chloride(s) with 2-hydroxy-5-methoxybenzaldehyde-N(4)-methyl-
thiosemicarbazone [H
complexes, namely, [MeSnCl(dmmt)] (2), [BuSnCl(dmmt)] (3), [PhSnCl(dmmt)] (4), and [Ph
5). The new compounds were characterized using CHN analyses, molar conductivity, UVeVis, FTeIR, and
2
dmmt, (1)] in the presence of potassium hydroxide yielded four new stable
2
Sn(dmmt)]
11 March 2016
(
Accepted 10 April 2016
Available online 13 April 2016
1
13
119
2
H, C, and Sn NMR spectral studies. The molecular structures of H dmmt (1) and its complex 5 were
determined using X-ray crystallography. The X-ray crystal studies of complex 5 showed the trigonal
bipyramidal geometry around the tin(IV) atom. The solid-state structure of complex 5 revealed that the
dinegative tridentate ligand (1) is coordinated with the tin(IV) moiety via phenolic-O, azomethine-N, and
thiolate-S atoms. The biological activities of the organotin(IV) complexes were investigated against a
human colorectal (HCT 116) cell line and exhibited strong cytotoxic activities in the following order:
Keywords:
2-Hydroxy-5-methoxybenzaldehyde-N(4)-
methylthiosemicarbazone
Organotin(IV) complexes
Spectral characterization
Crystal structure
5 > 4 > 2 > 3 > H
with the standard drug, 5-fluorouracil (IC50 ¼ 7.58
results show that organotin(IV) complexes may be designed as new metal-based drugs in the future.
2016 Published by Elsevier B.V.
2
dmmt. The organotin(IV) complexes (2e5) showed significant activity when compared
m
M), and the parent ligand (IC50 ¼ 7.19 M). These
m
Cytotoxic activity
©
1
. Introduction
ONS donor thiosemicarbazones have received significant interest
for their coordination chemistry and various applications, such as
antibacterial, antifungal, cytotoxic, and biocidal agents [16e18].
These complexes were also greatly studied because of their struc-
tural diversity and the coordination number of the tin(IV) moiety
[19,20]. Khandani et al., reported the diorganotin(IV) complexes of
3-methoxysalicylaldehyde thiosemicarbazone, which have five
coordinated complexes and exhibit significant cytotoxic and anti-
bacterial activities [21]. Moreover, the electronic and steric features
of organic groups bonded to tin(IV) moiety considerably influence
the structures of organotin(IV) complexes [22]. We recently studied
the structural and biological activities of tridentate ONS-donor
thiosemicarbazones and their organotin(IV) complexes [23,24].
Results showed that thiosemicarbazone ligands and their corre-
sponding organotin(IV) complexes exhibit indicative biological
activities. After a careful literature survey, we can state that orga-
notin(IV) complexes with tridentate ONS-donor thiosemicarbazone
are still lacking. As part of our research, we report the synthesis,
spectroscopic characterization, and antitumor activities of orga-
notin(IV) complexes of 2-hydroxy-5-methoxybenzaldehyde-N(4)-
Thiosemicarbazone has attracted numerous studies because of
its chelating capability, versatile coordination nature, and various
pharmacological properties [1,2]. Thiosemicarbazone generally
behaves as a chelating agent with particular metal ions, bonding via
ꢀ
ꢀ
the thiolate S and hydrazine N atoms [3]. It is an important
multidentate chelating agent that shows useful biological activities,
including antitumor, antiviral, antitubercular, antibacterial, and
antimalarial properties [4e9]. The tridentate ONS-donor contain-
ing thiosemicarbazones, which are used in coordination chemistry,
easily forms complexes with most metal ions [10e12]. Thio-
semicarbazone derivatives with transition and main group metals
present significant biological properties [13e15] and promise a
new opportunity to develop the extent of these metal complexes in
various medicinal fields. Organotin(IV) complexes with tridentate
*
Corresponding author.
E-mail addresses: salambpx@yahoo.com, salam@bapex.com.bd (M.A. Salam).
http://dx.doi.org/10.1016/j.jorganchem.2016.04.007
022-328X/© 2016 Published by Elsevier B.V.
0

72
M.A. Salam et al. / Journal of Organometallic Chemistry 813 (2016) 71e77
methylthiosemicarbazone. In addition, single-crystal X-ray crystal
structures of the ligand and its single representative complex are
also reported.
ppm): 188.40 (C]S), 156.94 (C]N), 146.04, 132.55, 124.81, 122.95,
117.55, 112.42 (PheC), 64.14 (OCH ), 30.60 (CH ). Anal. Calc. for
S: C, 50.19; H, 5.48; N, 17.56. Found: C, 50.11; H, 5.37; N,
3
3
10 13 3 2
C H N O
17.44%.
2
. Experimental
2.3. Synthesis of [MeSnCl(dmmt)] (2)
2.1. Materials and methods
A methanolic solution of MeSnCl
dropwise to a methanolic solution (10 mL) of H dmmt (1) (0.239 g,
3
(0.24 g, 1.0 mmol) was added
All reagents were purchased from Fluka, Sigma, and Aldrich. All
2
solvents were received as reagent grade and used without further
purification. Melting point was measured using a Stuart Scientific
SMP1 melting point apparatus. UVeVis spectra were recorded in
DMSO with a Perkin-Elmer Lambda 25 UVeVis spectrophotometer.
FTeIR spectra were recorded on a Perkin-Elmer System 2000
1.0 mmol) and KOH (0.11 g, 2.0 mmol). The reaction mixture was
heated at reflux for 4 h under nitrogen atmosphere (Scheme 2) and
then allowed to cool slowly to room temperature. KCl was filtered
off and the solution was dried in a desiccator over anhydrous silica
gel. Yellow solids were purified by recrystallization from methanol,
and dried in vacuo over silica gel. Yield: 0.37 g, 77%; mp
ꢀ1
spectrophotometer in KBr pellet in the 4000e400 cm range at
1
13
119
ꢀ3 ꢀ1
ꢁ
room temperature. H, C, and Sn NMR spectra were recorded on
a Bruker 500 and 400 MHz NMR spectrophotometer, relative to
SiMe and SnMe in DMSO-d . Elemental analysis was conducted
230e232 C; molar conductivity (1 ꢂ 10
mol L ; DMSO)
ꢀ1
2
ꢀ1
d
U
cm mol : 10.15; UVeVis (DMSO) lmax/nm: 258, 342, 355,
408; FTeIR (KBr) n/cm : 3160 (s, NH), 1582 (m, C]N), 1525 (s,
ꢀ1
4
4
6
using a Perkin-Elmer 2400 Series-11 CHN analyzer. Molar con-
ductivity measurements were performed with a Jenway 4510
conductivity meter using DMSO as solvent. X-ray crystallographic
data were recorded on a Bruker SMART APEXII CCD area-detector
CaroeO), 1024 (m, NeN), 1325, 842 (w, CeS), 593 (w, SneC), 555 (w,
1
SneO), 468 (w, SneN); H NMR (500 MHz, DMSO-d , ppm): 8.81 (s,
6
1H, CSeNH), 8.30 (s, 1H, CH]N), 7.75 (d, 1H, J ¼ 7.4, PhC3eH), 7.11
(d, 1H, J ¼ 7.6, PhC4eH), 6.71 (s, 1H, PhC6eH), 4.06 (s, 3H, OCH ),
3
13
diffractometer using graphite monochromated MoK
a
radiation
3 3
3.08 (s, 3H, CH ), 1.12 (s, 3H, SneCH ); C NMR (125 MHz, DMSO-
(
l
¼ 0.71073 Å) at 100 K. Data were collected and reduced using
d6, ppm): 172.12 (C]S), 163.84 (C]N), 149.03, 140.72, 134.55,
132.65, 127.33, 120.01 (PheC), 64.88 (OCH ), 30.90 (CH ), 17.24
APEX2 and SAINT programs. The structures were solved through
direct methods and refined using full-matrix least-squares method
on F using the SHELXTL program [25]. All non-H atoms were
3
3
119
(SneCH );
3
Sn NMR (DMSO-d , ppm): ꢀ178.25. Anal. Calc. for
6
2
3 2
C11H14ClN O SSn: C, 32.50; H, 3.47; N, 10.34. Found: C, 32.41; H,
anisotropically refined. The molecular graphics were created using
3.33; N, 10.15%.
SHELXTL-97.
The other complexes (3e5) were synthesized through a similar
procedure to organotin(IV) complex (2) using appropriate orga-
notin(IV) chloride(s) (Scheme 2).
2
2.2. Synthesis of H dmmt (1)
A
solution of 2-hydroxy-5-methoxybenzaldehyde (0.60 g,
2.4. Synthesis of [BuSnCl(dmmt)] (3)
4
.0 mmol) in methanol (10 mL) was treated with a methanolic
solution (10 mL) of 4-methylthiosemicarbazide (0.42 g, 4.0 mmol).
The resulting reaction mixture was refluxed with stirring for 4 h
ꢁ
Yield: 0.41 g, 78%; mp 238e240 C; molar conductivity
ꢀ3
ꢀ1
ꢀ1
2
ꢀ1
(
l
(
(
1 ꢂ 10 mol L ; DMSO)
U
cm mol : 9.25; UVeVis (DMSO)
(Scheme 1). A white fluffy product was formed when the solution
ꢀ1
max/nm: 265, 335, 359, 404; FTeIR (KBr)
n
/cm 3158 (s, NH), 1580
cooled down to room temperature. The product was filtered,
washed with methanol, and dried in desiccators over silica gel.
Yield: 0.78 g, 76%; mp 197e199 C; UVeVis (DMSO)
m, C]N), 1510 (s, CaroeO), 1028 (m, NeN), 1322, 837 (w, CeS), 590
w, SneC), 556 (w, SneO), 454 (w, SneN); H NMR (500 MHz,
1
ꢁ
l
max/nm: 262,
DMSO-d
H, J ¼ 7.5, PhC3eH), 7.17 (d, 1H, J ¼ 7.3, PhC4eH), 6.70 (s, 1H,
PhC6eH), 4.08 (s, 3H, OCH ), 3.07 (s, 3H, CH ), 1.64e1.57 (t, 2H,
SneCH eCH eCH eCH ), 1.37e1.28 (m, 2H, SneCH eCH e-
CH eCH ), 1.22e1.14 (m, 2H, SneCH eCH eCH eCH ), 0.98e0.91
t, 3H, SneCH ); C NMR (125 MHz, DMSO-d
ppm): 170.42 (C]S), 168.35 (C]N), 150.34, 141.22, 133.11, 131.58,
28.10, 121.25 (PheC), 65.01 (OCH ), 31.05 (CH ), 24.08, 21.08, 19.12,
6
, ppm): 8.78 (s, 1H, CSeNH), 8.40 (s, 1H, CH]N), 7.72 (d,
ꢀ
1
3
28, 361; FTeIR (KBr)
m, C]N), 1559 (s, CaroeO), 985 (m, NeN), 1365, 861 (w, CeS); H
NMR (500 MHz, DMSO-d , ppm): 11.56 (s, 1H, OH), 10.38 (s, 1H,
n
/cm : 3369 (s, OH), 3207, 3155 (s, NH),1620
1
1
(
3
3
6
2
2
2
3
2
2
NeNH), 8.79 (s, 1H, CSeNH), 8.41 (s, 1H, CH]N), 7.49 (d, 1H, J ¼ 7.2,
2
3
2
2
2
3
PhC3eH), 6.96 (d, 1H, J ¼ 7.5, PhC4eH), 6.75 (s, 1H, PhC6eH), 4.04
13
(
2
eCH
2
eCH
2
eCH
3
6
,
13
(
3 3 6
s, 3H, OCH ), 3.01 (s, 3H, CH ); C NMR (125 MHz, DMSO-d ,
1
3
3
Scheme
1. Synthesis
of
2-hydroxy-5-methoxybenzaldehyde-N(4)-methyl-
thiosemicarbazone (H
2
dmmt) (1).
Scheme 2. Reaction scheme for the synthesis of organotin(IV) complexes (2e5).

M.A. Salam et al. / Journal of Organometallic Chemistry 813 (2016) 71e77
73
1
7.53
(SneCH
2
eCH
2
eCH
2
eCH
3
);
H
119Sn
NMR
(DMSO-d
6
,
The purity of compounds 1e5 were confirmed using elemental
analysis and spectroscopic studies. All products were yellow solids,
air stable, and soluble in common organic solvents, such as MeOH,
ppm): ꢀ170.44. Anal. Calc. for C14
20ClN
3
O
2
SSn: C, 37.49; H, 4.49;
N, 9.37. Found: C, 37.38; H, 4.41; N, 9.15%.
CHCl
3 2 2
, CH Cl , DMF, and DMSO. These products were also obtained
2
.5. Synthesis of [PhSnCl(dmmt)] (4)
with a good percentage of yields (81%e76%). Their molar conduc-
ꢀ ꢀ1
1
2
tance values of 12.08e9.25
U
cm mol in DMSO indicate their
ꢁ
ꢀ1
Yield: 0.44 g, 81%; mp 241e243 C; molar conductivity
non-electrolytic nature [27]. The physico-chemical data of the
products are presented in Section 2.
ꢀ3
ꢀ1
ꢀ1
2
(
1 ꢂ 10 mol L ; DMSO)
U
cm mol : 11.38; UVeVis (DMSO)
ꢀ
1
l
max/nm: 261, 333, 357, 416; FTeIR (KBr) n/cm : 3150 (s, NH), 1584
(
(
m, C]N), 1517 (s, CaroeO), 1027 (m, NeN), 1318, 841 (w, CeS), 588
w, SneC), 548 (w, SneO), 472 (w, SneN); H NMR (500 MHz,
3.2. UVevisible spectra
1
DMSO-d
6
, ppm): 8.70 (s, 1H, CSeNH), 8.37 (s,1H, CH]N), 7.79e6.74
The electronic spectra of compounds 1e5 were measured in
13
ꢀ4
ꢀ1
(
(
1
(
m, 8H, PheH), 4.11 (s, 3H, OCH
125 MHz, DMSO-d ppm): 175.32 (C]S), 162.81(C]N),
51.11e120.55 (Ph-C), 64.21 (OCH
DMSO-d
, ppm): ꢀ164.23. Anal. Calc. for C16
3
), 3.11 (s, 3H, CH
3
); C NMR
DMSO (1 ꢂ 10 mol L ) at room temperature. In the electronic
spectrum of H dmmt (1), three absorption bands were observed at
262, 328, and 361 nm; these bands may be assigned to * and
ne * transitions of the aromatic ring and the thiosemicarbazone
6
,
2
119
3
), 30.82 (CH
3
);
Sn NMR
SSn: C,
pep
6
H16ClN
3
O
2
p
4
1.02; H, 3.44; N, 8.97. Found: C, 40.88; H, 3.32; N, 8.80%.
moiety [28]. These bands were slightly shifted on complexation. A
new sharp band was observed at the 428e412 nm region in the
electronic spectra of complexes (2e5) and assigned as ligand-to-
metal charge transfer [29].
2.6. Synthesis of [Ph
2
Sn(dmmt)] (5)
ꢁ
Yield: 0.46 g, 79%; mp 253e255 C; molar conductivity
ꢀ
3
ꢀ1
ꢀ1
2
ꢀ1
(
l
1 ꢂ 10 mol L ; DMSO)
U
cm mol : 12.08; UVeVis (DMSO)
3.3. Infrared (IR) spectra
ꢀ1
max/nm: 260, 330, 358, 411; FTeIR (KBr) n/cm : 3162 (s, NH),1585
(
(
m, C]N), 1542 (s, CaroeO), 1034 (m, NeN), 1328, 843 (w, CeS), 587
w, SneC), 558 (w, SneO), 470 (w, SneN); H NMR (500 MHz,
The IR spectrum of H
and 3202 cm , which were caused by the stretching vibrations of
2
dmmt (1) showed broad bands at 3334
1
ꢀ1
ꢀ1
DMSO-d
6
, ppm): 8.72 (s,1H, CSeNH), 8.33 (s,1H, CH]N), 7.62e6.72
the OH and NH groups respectively. Medium bands at 1620 cm
were attributed to (C]N) and a very strong absorption at
1559 cm , which can be assigned to the (CaroeO) group. The other
bands observed in the spectrum of ligand (1) at 1014, 1385, and
13
(
(
1
(
m, 13H, PheH), 4.12 (s, 3H, OCH
125 MHz, DMSO-d ppm): 171.92 (C]S), 163.41 (C]N),
50.23e122.33 (PheC), 65.15 (OCH
DMSO-d
, ppm): ꢀ168.40. Anal. Calc. for C22
H, 4.15; N, 8.24. Found: C, 52.61; H, 4.02; N, 8.13%.
3
), 3.05 (s, 3H, CH
3
); C NMR
n
ꢀ1
6
,
n
119
3
), 30.91 (CH
3
);
Sn NMR
ꢀ
1
6
H
21
N
3
O
2
SSn: C, 51.79;
861 cm were caused by (NeN) and n(C]S). The n(OH) and NH
bands disappeared upon complexation, indicating that ligand (1)
was coordinated through the phenolic oxygen and thiolate sulfur
2.7. Evaluation of cytotoxic effect by MTT assays
atoms [30]. In particular, the n(C]N) and n(CaroeO) absorption
bands shifted to lower frequencies in the spectra of complexes
(2e5) compared with those of free ligand (1), indicating the coor-
dination of the azomethine nitrogen and phenolic oxygen atoms to
The cytotoxic effects of 1e5 against a human colorectal cancer
HCT 116) cell line were evaluated using MTT assay procedures [26].
(
5
Human colorectal cancer (HCT 116) cell lines (1.5 ꢂ 10 cells/mL,
00 L/well) were seeded in a 96-well microtiter plate. The plate
was incubated in a CO incubator overnight to allow cell attach-
ment. A total of 24 h after seeding, the cells in each well were
incubated with 100 L of the test organotin(IV) complexes. Test
the tin(IV) moiety [31,32]. The n(NeN) band appeared at higher
1
m
frequencies in the IR spectra of the complexes compared with those
observed for the free ligand, which confirmed the coordination via
the azomethine nitrogen atom [33]. The stretching and bending
2
ꢀ
1
m
vibration of n(C]S) band at 1365 and 861 cm in the spectra of
ꢀ
1
compounds were diluted with media into various concentrations
free ligand (1) was shifted to lower frequencies at 1328e1322 cm
ꢁ
ꢀ1
from the stock. The plates were incubated at 37 C with an internal
and 843e837 cm ranges in the complexes (2e5). This behavior
atmosphere of 5% CO
was added into each well, and the plates were incubated for 4 h.
After this incubation period, 50 L of MTT lysis solution (DMSO)
was added into the wells. The plates were further incubated for
min in a CO incubator. Finally, the absorbance was measured at
70 nm using a standard ELISA microplate reader. Data were
2
for three days. Then, 20
m
L of MTT reagent
indicated the coordination through the sulfur atom [34]. The new
ꢀ
1
ꢀ1
band that appeared between 593 cm and 587 cm in complexes
(2e5) was attributed to (SneC) vibrations [35]. The two absorp-
tion bands observed in the ranges of 558e548 cm
m
n
ꢀ1
and
472e454 cm in the spectra of complexes (2e5) were assigned to
(SneO) and (SneN) mode respectively.
ꢀ
1
5
5
2
n
n
recorded and analyzed to assess the effects of the test compound on
cell viability. The drug concentration required to reduce the cell
number to 50% of the controls following a 72 h continuous drug
3.4. 1H, 13C and 119Sn NMR spectra
exposure (IC50
)
was obtained from semi-logarithmic dos-
The NMR spectral assignments of free ligand (1) and its orga-
notin(IV) complexes (2e5) were conducted and interpreted based
on the atom labeling in Scheme 2. The single resonance of OH in
free ligand (1) disappeared in the spectra of complexes (2e5),
indicating that phenolic oxygen is coordinated to tin(IV) atom. The
absence of an NeNH signal in the spectra of the complexes (2e5)
suggested that the thionic form of the ligand was coordinated to the
tin(IV) core after deprotonation. The N]CH signal shifted down-
field in complexes (2e5), which strongly suggests coordination via
azomethine nitrogen. The phenolic proton signal shifted to a lower
field in the complexes compared with free ligand because of co-
ordination. The resonance signal of the CSeNH proton appeared at
the expected region in ligand (1) and its complexes (2e5). The
eeresponse plots. The medium without samples served as control.
All tests were performed in triplicate.
3
. Results and discussion
3.1. Synthesis
The 2-hydroxy-5-methoxybenzaldehyde reacts with 4-
methylthiosemicarbazide in methanol to form
2
H dmmt (1).
H
2
dmmt (1) is a potent tridentate ONS-donor ligand that can form
coordination complexes with organotin(IV) chloride(s) in the
presence of KOH in 1:2:1 M ratio (metal: base: ligand) (Scheme 2).

74
M.A. Salam et al. / Journal of Organometallic Chemistry 813 (2016) 71e77
methoxy group attached to the phenyl ring presented
a
singlet almost in the same region where the complexes and their
ligands were.
In 13C NMR, the carbon signal of the (C]S) group shifted to the
upfield region in complexes (2e5) compared with the free ligand,
-
which supported the coordination through N]CeS group with
tin(IV) atom. The chemical shifts of (C]N) carbon was shifted to the
downfield region in the complexes compared with the free ligand,
which supported coordination through the azomethine nitrogen
atom to tin(IV) moiety. The phenolic carbon signals of all complexes
were observed in the downfield region in comparison with the free
ligand (1), indicating that phenolic ring oxygen was coordinating
3 3
with tin(IV) atom. Signals caused by the (NeCH ) and (eOCH )
were observed approximately in the same region as the ligand and
their complexes.
The 1 Sn NMR chemical shift of the organotin(IV) complexes
19
119
(
2e5) was obtained in DMSO. Sn NMR spectra of all complexes
exhibited a single signal from the ꢀ178.25 ppm to ꢀ164.23 ppm
range, which is compatible with penta-coordinated Sn(IV) atom
[36,37].
2
Fig. 2. The packing diagram of H dmmt (1) in the crystal lattice. Intermolecular
hydrogen bonds are shown as dotted lines.
3
.5. Crystallographic analyses of H dmmt (1)
2
The corresponding molecular structures of H
crystal packing are given in Figs. 1 and 2. The crystal data and
structure refinement parameters for H dmmt (1) are shown in
Table 1. Selected bond lengths and bond angles are listed in Table 2.
A single crystal suitable for X-ray analysis was obtained from
2
dmmt (1) and its
analogous dimers via the intermolecular hydrogen bonds
N2eH1/O1 [symmetry code, x, y, ꢀ1 þ z] and C10eH1A/O2
[symmetry code, x, 3/2 ꢀ y, ꢀ1/2 þ z]. These hydrogen bonds
2
permit the H dmmt (1) molecules to be stacked along the a-axis,
2
and thus stabilize the crystal packing structure. Furthermore, the
methanol at RT. The title compound C10
monoclinic lattice with the space group P2
structure of H dmmt (1) showed the trans geometries of the S1
atom in relation to the N1 atom, and the C8 atom in relation to the
N2 atom. Similarly, H dmmt (1) exhibited the syn geometries of the
N1 atom in relation to the N3 atom, and the C8 atom in relation to
the S1 atom. In H dmmt (1), the bond distances of S1eC8 and
H
13
N
3
O
2
crystallized into
orientation of the aromatic ring moiety [torsion angle
ꢁ
1
/c. The molecular
C1eC6eC7eN1 ¼ ꢀ3.18(15) ] was stabilized by the intramolecular
2
O1eH1/N1 hydrogen bond.
2
2
3.6. Crystallographic analyses of [Ph Sn(dmmt)] (5)
2
Suitable yellow single crystals of diphenyltin(IV) complex 5 for
X-ray analysis were obtained through slow evaporation of a
methanol solution at room temperature. Fig. 3 shows the molecular
N1eC7 were 1.6853(10) Å and 1.2888(13) Å respectively. These
bond lengths were also expected in the C]S double bond (1.60 Å)
[
38] and the C]N double bond (1.28 Å) [39]. These values
confirmed that H dmmt (1) is in tautomeric thione form in solid
state. H dmmt (1) may be divided into two planar portions joined
2
structure of [Ph Sn(dmmt)] (5) along with the atom numbering
2
scheme. Crystal data and structure refinement details are given in
Table 1, and important bond distances and angles are provided in
Table 2. The compound crystallized into a triclinic system with a
space group of P-1. Based on the crystal structure, the doubly
deprotonated ligand was bonded to tin(IV) atom as an ONS-
tridentate chelating agent via the phenolic oxygen O(1), azome-
thine nitrogen N(1), and thiolato sulfur S(1) atoms. The crystal
structure revealed that the tin atom is penta-coordinated, which is
described as a distorted trigonal bipyramidal geometry with N(1),
C(1), and C(7) atoms occupying the equatorial positions and O(1)
2
by an N1eN2 single bond. The first plane, N-methylthioureide
plane, contains N2, S1, N3, C8, and C9 atoms; and the second plane,
salicylaldimine plane, contains N1, O1, O2, C1eC7, and C10 atoms.
ꢁ
The dihedral angle of these two planes is 14.39(19) . The O2 and
C10 atoms of the methoxy group were in the same plane as the
ꢁ
salicylaldimine fragment, which was inclined by 173.78(10) . The
2
crystal structure of H dmmt (1) formed centrosymmetrically
and S(1) atoms occupying the axial positions. The sum of the
ꢁ
equatorial
angle
[C1eSn1eC7
¼
120.10(5) ,
ꢁ
ꢁ
C1eSn1eN1 ¼ 106.89(5) , and N1eSn1eC10 ¼ 132.94(5) ] is
ꢁ
3
59.93 . Therefore, the Sn(IV) atom displayed no significant devi-
ation from the equatorial plane. The coordinated part of the ONS-
tridentate ligand was composed of five- and six-membered
chelate rings, such as Sn1eS1eC21eN2eN1 (I) and Sn1eO1e-
C13eC18eC20eN1 (II). The bond angles between the planes of the
ꢁ
two rings (I and II) were C1eSn1eC7 (120.10 ), C7eSn1eN1
ꢁ
ꢁ
(
132.94 ), and C1eSn1eN1 (106.89 ) for C1, C7, and N1 atoms were
placed at the three edges of the trigonal plane, indicate for the
deviation from the regular TBP. The deviation from the ideal
trigonal bipyramidal configuration is shown by the bond angle of
ꢁ
ꢁ
S1eSn1eN1 at 77.91(3) and O1eSn1eN1 at 82.85(4) . The sum of
Fig. 1. Molecular structure of 2-hydroxy-5-methoxybenzaldehyde-N(4)-methyl-
ꢁ
ꢁ
these angles is 160.76 , which deviated considerably from 180 . In
addition, the bond angle of C7eSn1eN1 was 132.94(5) , which is
thiosemicarbazone [H
bility level.
2
dmmt, (1)] showing displacement ellipsoids at the 50% proba-
ꢁ

M.A. Salam et al. / Journal of Organometallic Chemistry 813 (2016) 71e77
75
Table 1
2
Crystal data and structure refinement parameters for H dmmt (1) and [Ph
2
Sn(dmmt)] (5).
Compound
H
2
dmmt (1)
[Ph
2
Sn(dmmt)] (5)
Empirical formula
Formula weight
T (K)
C
10
H
13
3
N O
2
S
C H N O SSn
510.17
100
22 21 3 2
239.29
100(2)
l
(Å)
0.71073
monoclinic
P2 /c
0.71073
triclinic
P-1
Crystal system
Space group
Unit cell dimensions
a (Å)
1
7.0800(3)
9.7854(9)
9.8577(9)
b (Å)
24.6000(10)
6.3013(3)
90.00
94.5350(10)
90.00
1094.05(8)
4
1.453
c (Å)
12.0224(11)
109.413(1)
104.664(1)
98.379(1)
1024.01(16)
2
ꢁ
a
b
g
( )
ꢁ
( )
ꢁ
( )
3
V (Å )
Z
3
Calculated density (mg/m )
1.655
Radiation type
F(000)
l(Å)
MoK\
504
a
MoK\
512
a
Crystal size (mm)
0.109 ꢂ 0.158 x 0.336
0.195 ꢂ 0.374 x 0.456
Crystal colour
yellow
yellow
ꢁ
Scan range
q
( )
2.89e31.09
0.285
2.32e30.15
1.373
Absorption coefficient (
m
) (mmꢀ1)
Max. and min. transm
Goodness-of-fit (GOF) on F
0.970 and 0.910
1.048
0.543 and 0.886
1.054
2
Data/Restrains/parameters
3548/0/159
6040/0/268
Final R indices [I > 2
R indices (all data)
s(I)]
R
R
1
1
¼ 0.0329, wR
2
2
¼ 0.0824
¼ 0.0855
R
R
1
1
¼ 0.0194, wR
2
2
¼ 0.0470
¼ 0.0485
¼ 0.0379, wR
¼ 0.0213, wR
Table 2
ꢁ
Selected bond lengths (Å) and angles ( ) of H
2
dmmt (1) and [Ph
2
Sn(dmmt)] (5).
Bond lengths (Å)
H
2
dmmt (1)
2
[Ph Sn(dmmt)] (5)
S1eC8
O1eC1
O2eC4
O2eC10
N1eN2
N1eC7
N2eC8
N3eC8
N3eC9
C1eC2
C1eC6
1.6853(11)
1.3685(12)
1.3670(12)
1.4248(14)
1.3821(12)
1.2887(14)
1.3639(14)
1.3242(14)
1.4534(14)
1.3919(14)
1.3995(13)
Sn1eS1
Sn1eN1
Sn1eC7
O1eC13
N1eC20
N3eC21
O2eC16
Sn1eO1
Sn1eC1
S1eC21
N1eN2
2.5255(5)
2.2236(13)
2.1397(16)
1.3311(18)
1.3067(19)
1.3581(19)
1.3783(19)
2.0641(10)
2.1319(16)
1.7509(15)
1.3887(17)
ꢁ
Bond angles ( )
dmmt (1)
H
2
2
[Ph Sn(dmmt)] (5)
C4eO2eC10
N2eN1eC7
N1eN2eC8
C8eN3eC9
O1eC1eC2
O1eC1eC6
C2eC1eC6
C1eC2eC3
C2eC3eC4
C3eC4eC5
O2eC4eC5
N1eC7eC6
S1eC8eN3
N2eC8eN3
117.33(8)
114.26(8)
120.73(9)
123.50(9)
117.95(8)
122.40(9)
119.65(9)
120.61(9)
120.27(9)
119.76(9)
125.11(9)
123.35(9)
124.32(8)
117.41(9)
S1eSn1eO1
S1eSn1eC1
O1eSn1eN1
O1eSn1eC7
N1eSn1eC7
Sn1eS1eC21
Sn1eN1eN2
S1eSn1eN1
S1eSn1eC7
O1eSn1eC1
N1eSn1eC1
C1eSn1eC7
Sn1eO1eC13
Sn1eN1eC20
155.78(3)
102.37(4)
82.85(4)
88.53(5)
132.93(5)
96.13(5)
121.95(9)
77.91(3)
93.84(4)
97.18(5)
106.89(5)
120.10(6)
129.93(9)
124.98(10)
2
Fig. 3. Molecular structure of [Ph Sn(dmmt)] (5) showing displacement ellipsoids at
the 50% probability level.
indicating that the two phenyl groups were not executed for de-
viation. The Sn1eS1 bond length was 2.5255(4) Å, which is close to
the sum of the covalent radii of Sn and S (2.42 Å) [40], indicating a
strong SneS bond. The Sn1eO1 and Sn1eN1 bond lengths were
2
.0641(10) Å and 2.2236(12) Å, respectively, which are close to the
sum of the covalent radii of SneO (2.10 Å) and SneN (2.15 Å)
41,42]. This finding suggests the strong coordinate covalent bond
between Sn and phenolic-O and azomethine-N. The respective
Sn1eC1 and Sn1eC7 bond distances at 2.1319(14) and
.1396(14) Å are similar to those of other published organotin(IV)
compounds [43,44]. The geometry around tin atom can be best
defined by the value that can be calculated from the equation,
¼ ( )/60, where is the largest basal angle around the tin atom
while is the next largest angle around tin [45,46]. The value is
zero for an ideal square-pyramidal and unity for ideal trigonal-
[
ꢁ
smaller than 180 . The deviation was most possibly caused by the
contribution of the azomethine N1 atom in the five-membered
chelate rings and larger Sn(IV) size. The O1 and S1 atoms that co-
ordinated with the Sn(IV) centre occupied apical positions; the
Å
2
t
ꢁ
angle of S1eSn1eO1 was 155.78(3) , which deviated from ideal
t
b
ꢀ
a
a
b
ꢁ
1
80 . The two phenyl groups were bonded to tin(IV) atom and the
t
ꢁ
ꢁ
angle of C1eSn1eC7 was 120.10(5) ). This angle was close to 120 ,

76
M.A. Salam et al. / Journal of Organometallic Chemistry 813 (2016) 71e77
bipyramidal geometry. The calculated
which confirm distorted trigonal-bipyramidal geometry around tin
47]. The packing in the crystal lattice of complex 5 is shown in
Fig. 4. The chains were packed in the ac plane and stacked along the
b axis with links between layers afforded by NH…N hydrogen
bonds. The dimeric aggregates were connected by CeH … O1
t
value is 0.89 for complex 5,
Table 3
IC50 values (mM) for synthesized compounds 1e5 toward human colorectal cancer
(HCT 116) cell lines.
[
No.
Compound
IC50 (mM)
1
2
3
4
5
R
H dmmt
2
7.19
5.45
6.72
4.38
3.85
7.58
[MeSnCl(dmmt)]
[BuSnCl(dmmt)]
[PhSnCl(dmmt)]
hydrogen bond. The presence of additional CeH /
p and p / p
contacts further stabilized the crystal structure.
[Ph
2
Sn(dmmt)]
5-fluorouracil
2
Fig. 4. The packing diagram of [Ph Sn(dmmt)] (5) in the crystal lattice, viewed along the b axis.
3
.7. Cytotoxic activity
organotin(IV) complexes of 2-hydroxy-5-methoxybenzaldehyde-
N(4)-methylthiosemicarbazone [H dmmt, (1)] were studied. Based
on structural investigations, the H dmmt (1) was coordinated to
Sn(IV) moiety as a dinegative tridentate agent through the phenolic
O , azomethine N , and thiolate S atoms. The NMR spectra for
all organotin(IV) complexes authenticated penta-coordinated Sn
atom in solution. The in vitro cytotoxicity of the newly synthesized
ligand (1) and its organotin(IV) complexes (2e5) was investigated
against human colorectal cancer (HCT 116) cell lines. The activity
2
The anticancer tests were performed against the human colo-
2
rectal (HCT 116) cell line for all compounds. The IC50 values of
complexes and reference drug are presented in Table 3. The orga-
notin(IV) complexes (3e5) exhibited significant activity in compar-
ison with the parent ligand and the standard drug, 5-fluorouracil.
IC50 value of reference drug (5-fluorouracil) is 7.58
and 4 showed higher anticancer activities with IC50 values of 3.85
and 4.38 M respectively compared with other organotin(IV) com-
plexes. This finding indicated that the bulky phenyl group attached
to the tin(IV) centre of the same ligand exhibited enhanced anti-
cancer activity [48]. The antiproliferative efficiency was explained in
ꢀ
ꢀ
ꢀ
119
mM. Complexes 5
m
decreased in the following order: 5 > 4 > 2 > 3 > H
corresponds to their IC50 values at 3.85, 4.38, 5.45, 6.72, and
7.19 M, respectively. This study show that the nature of R groups
bonded to tin(IV) atom showed distinctive differences in the bio-
2
dmmt, which
m
2
the following order: 5 > 4 > 2 > 3 > H dmmt. This observation
2
logical activities in the order of Ph > Ph > Me > Bu>.
suggested that the activity of the studied compound is dependent on
the organo group attached to the tin(IV) atom in the order
Ph
played remarkable activity against the human colorectal cancer (HCT
16) cell lines when the cytotoxicity of the studied compounds were
2
> Ph > Me > Bu. However, the organotin(IV) complexes dis-
Acknowledgment
1
M.A.S. thanks Bangladesh Petroleum Exploration and Produc-
tion Co., Ltd., Dhaka, Bangladesh, for all supports.
compared with that of the reference 5-fluorouracil drug. The bio-
logical activities of all organotin(IV) complexes are comparable with
the recently published organotin complexes [49,50]. The above
biological investigation also suggests that the activity is mainly
influenced by the types of organic groups on tin, diffusion, lipophilic,
and steric effects [51]. The results suggest that organotin(IV) com-
plexes possess significant anticancer activity and may lead to more
promising metal complexes.
Appendix A. Supplementary data
CCDC 1400814 and 1061610 contain the supplementary crys-
tallographic data for H dmmt (1) and [Ph Sn(dmmt)] (5). These
2 2
data can be obtained free of charge from the Cambridge Crystal-
lographic Data Centre website via www.ccdc.ac.uk/data_request/cif
or from the Cambridge Crystallographic Data Centre at 12 Union
Road, Cambridge CB2 1EZ, UK; fax number: (þ44) 1223-336-033;
or e-mail: deposit@ccdc.cam.ac.uk.
4
. Conclusion
The synthesis, characterization, and cytotoxic activity of

M.A. Salam et al. / Journal of Organometallic Chemistry 813 (2016) 71e77
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