Synthesis, spectroscopic characterization, structural studies and antibacterial and antitumor activities of diorganotin complexes with 3-methoxysalicylaldehyde thiosemicarbazone

Article abstract of DOI:10.1016/j.molstruc.2012.12.061

Three organotin(IV) complexes, Ph₂Sn(mstsc) (1), Me ₂Sn(mstsc) (2) and Bu₂Sn(mstsc) (3), have been synthesized from reaction of R₂SnCl₂ (R = Ph, Me and Bu) with 3-methoxysalicylaldehyde thiosemicarbaz

Full text of DOI:10.1016/j.molstruc.2012.12.061

Journal of Molecular Structure 1037 (2013) 136–143
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis, spectroscopic characterization, structural studies and antibacterial
and antitumor activities of diorganotin complexes with
3-methoxysalicylaldehyde thiosemicarbazone
c
c
Marzieh Khandani a, Tahereh Sedaghat b, , Nasrollah Erfani , Mohammad Reza Haghshenas ,
⇑
Hamid Reza Khavasi d
a Department of Chemistry, Science and Research Branch, Islamic Azad University, Khouzestan, Iran
b Department of Chemistry, College of Sciences, Shahid Chamran University, Ahvaz, Iran
c Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, P.O. Box: 71345-3119, Shiraz, Iran
d Department of Chemistry, Shahid Beheshti University, G. C., Evin, Tehran 1983963113, Iran
g r a p h i c a l a b s t r a c t
h i g h l i g h t s
"
Synthesis of three diorganotin(IV)
complexes with a
thiosemicarbazone.
"
Geometry for dimethyl and dibutyl
complexes is distorted square
pyramid.
"
"
Dimethyltin complex exhibits good
antibacterial activity.
Dibutyltin complex shows better
cytotoxicity against Jurkat cells.
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 August 2012
Received in revised form 19 December 2012
Accepted 21 December 2012
Available online 8 January 2013
Three organotin(IV) complexes, Ph2Sn(mstsc) (1), Me2Sn(mstsc) (2) and Bu2Sn(mstsc) (3), have been syn-
thesized from reaction of R2SnCl2 (R = Ph, Me and Bu) with 3-methoxysalicylaldehyde thiosemicarbazone
(H2mstsc). The synthesized complexes have been characterized by elemental analysis and FT-IR, 1H, 13C
and 119Sn NMR spectroscopy. The structures of 2 and 3 have been also confirmed by X-ray crystallogra-
phy. On the basis of spectral and structural data thiosemicarbazone acts as a tridentate dianionic ligand
and coordinates to tin through phenolic oxygen, the azomethine nitrogen and thiolate sulfur atoms. The
metal coordination geometry for 2 and 3 is described as distorted square pyramid and the crystal lattices
are stabilized by intermolecular hydrogen bands. On the basis of 119Sn NMR data, coordination number of
tin retains five in solution. The in vitro antibacterial activity of ligand and its complexes has been evalu-
ated against one Gram-positive and three Gram-negative bacteria. Complex 2 exhibited good activity
along with the standard antibacterial drugs. The in vitro cytotoxicities of the synthesized compounds
against Jurkat cells were evaluated by the standard WST-1 assay. The activity decreases in the order
3 > 1 > 2 = H2mstsc.
Keywords:
Organotin(IV)
Thiosemicarbazone
Antibacterial activity
Antitumor activity
Ó 2013 Elsevier B.V. All rights reserved.
⇑
Corresponding author. Fax: +98 611 3331042.
E-mail address: tsedaghat@scu.ac.ir (T. Sedaghat).
0022-2860/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molstruc.2012.12.061

M. Khandani et al. / Journal of Molecular Structure 1037 (2013) 136–143
137
2.2. Synthesis of 3-methoxysalicylaldehyde thiosemicarbazone
(H2mstsc)
1
NH2
H
N
4
10
2
3
9
8
N
5
6
H2mstsc was prepared according to a modified procedure
described in the literature [20]:
S
3-Methoxysalicylaldehyde (0.304 g, 2 mmol) and thiosemicar-
bazide (0.182 g, 2 mmol) were dissolved in methanol (15 mL).
Then two drops of acetic acid was added and the solution was re-
fluxed for 3 h. The resulting white product was filtered, washed
with methanol (2 ꢁ 5 mL) and dried in vacuum over CaCl2. Yield:
OH
7
OCH3
11
0.218 g, 96%; m.p. 208 °C; FT-IR (KBr, cmꢀ1):
m
(NAH), 3461, 3343,
(CAN), 1458; (CAO), 1262;
(C@S), 1120. 1H NMR (DMSO-d6) d: 11.39 (s, 1H, NH), 9.18
(s, 1H, OH), 8.39 (s, 1H, H4), 7.80 and 8.10 (2br s, 1H each, H1),
Fig. 1. Structure of H2mstsc with numbering for NMR assignments.
3166;
m(OAH), 3032;
m
(C@N), 1621;
m
m
m
3
3
7.52 (d, JHH = 7.8 Hz, 1H, H10), 6.95 (d, JHH = 8.0 Hz, 1H, H8), 6.76
1. Introduction
(t, JHH = 8.0 Hz, 1H, H9), 3.80 (s, 3H, H11). 13C NMR (DMSO-d6)
3
d: 53.87 (C11), 112.86 (C8), 118.17 (C10), 118.93 (C9), 120.74 (C5),
139.53 (C4), 145.97 (C6), 147.89 (C7), 177.72 (C2).
Thiosemicarbazones are an interesting group of multidentate
ligands because of their mixed hard–soft donor character and ver-
satile coordination behavior. These compounds have become a
subject of intense research interest since the discovery of their
cytotoxic activity against cancer cell and bacteriostatic effects
[1–3]. The biological properties of thiosemicarbazones are often
increased by metal ion coordination, for example lipophilicity
which controls the rate of entry into the cell is modified by coor-
dination and some side effects may decrease upon complexation.
This observation further encouraged detailed studies on coordina-
tion chemistry involving thiosemicarbazones [4–6]. One of the
interesting works in this field is synthesis and study of organo-
tin(IV) complexes of thiosemicarbazones. Interest to the chemis-
try of these complexes has stemmed from the wide range of
biomedical and commercial applications of organotin compounds,
including fungicides, bactericides, pesticides and antitumor agents
[7–11]. Among the non-platinum compounds exhibiting antican-
cer properties, organotin complexes have received considerable
attention. Up to now many organotin(IV) compounds have been
synthesized and tested for their antitumor activity and have been
found to be as effective as or even better than traditional heavy
metal anticancer drugs [12–14]. Recent studies have showed that
low doses of organotins can exhibit anti-tumoral activity and have
suggested an action mode via gene-mediated pathway in the can-
cer cells [11], although the toxicology of organotins to mammals
might limit clinical application of this class of complexes
[15,16]. Organotin(IV) complexes of thiosemicarbazone ligands
formed important series of organotin(IV) compounds and the
structural and biological studies of these compounds have been
increasingly reported [17–19]. This paper reports the synthesis,
spectral characterization and in vitro biological activity of three
2.3. Synthesis of Ph2Sn(mstsc) (1)
Triethylamine (0.5 mmol) was added to a stirring solution of H2-
mstsc (0.562 g, 0.25 mmol) in methanol (10 mL). This mixture was
stirred for 1 h at r.t. Then
a solution of Ph2SnCl2 (0.085 g,
0.25 mmol) in methanol (3 mL) was added. This solution was stir-
red for 1 h and then refluxed for 2 h. Then the solvent was evapo-
rated and the yellow product was collected, washed with methanol
(5 mL) and dried over CaCl2. Yield: 0.061 g (41%); m.p. 130 °C; Anal.
Calcd. for C21H19N3O2SSn: C, 49.85; H, 3.96; N, 8.24%. Found: C,
50.25; H, 3.83; N, 8.47%. FT-IR (KBr, cmꢀ1):
m(NAH), 3303–3150;
m
m
(C@N), 1647; m(CAS), 1072; m(CAO), 1555; m(SnAO), 597;
(SnAN), 453. 1H NMR (DMSO-d6): d = 8.46 [s, 3J(119SnA1H) =
3
44.0 Hz, 1H, H4], 7.04 (s, 2H, H1), 6.97 (d, JHH = 6.5 Hz, 1H, H10),
6.95 (d, JHH = 6.9 Hz, 1H, H8), 6.61 (t, JHH = 7.8 Hz, 1H, H9), 7.27
[m, 6H, Hmeta,para(SnPh2)], 7.68 [dd, JHH = 8.9, JHH = 1.5 Hz, 4H,
H
3
3
3
4
ortho(SnPh2), 3J(119SnA1H) = 83.2 Hz], 3.81 (s, 3H, H11). 13C NMR
(DMSO-d6) d: 56.27 (C11), 115.60 (C5), 115.89 (C8), 117.81 (C9),
125.34 (C10), 128.11 [Cmeta(SnPh2), 3J(119SnA13C) = 77.2 Hz],
128.73 [Cpara(SnPh2)], 134.83 [Cortho(SnPh2), J(119SnA13C) =
54.0 Hz], 147.47 [Cipso(SnPh2)], 151.10 (C4), 155.88 (C6), 155.98
(C7), 165.81 (C2). 119Sn{1H}NMR (DMSO-d6): d = ꢀ308.7.
2.4. Synthesis of Me2Sn(mstsc) (2)
Complex 2 was synthesized as described for 1 from Me2SnCl2
(0.055 g, 0.25 mmol). The yellow crystals suitable for X-ray crystal-
lography were obtained when the mother liquor was evaporated at
r.t. Yield: 0.054 g (48%); m.p. 156 °C; Anal. Calcd. for C11H15N3O2SSn:
C, 35.59; H, 3.91; N, 11.26%. Found: C, 35.52; H, 4.03; N, 11.30%. FT-IR
diorganotin(IV) complexes with
a thiosemicarbazone ligand,
3-methoxysalicylaldehyde thiosemicarbazone (H2mstsc), Fig. 1.
X-ray crystal structures of dimethyl and dibutyltin(IV) complexes
are also described.
(KBr, cmꢀ1):
(CAO), 1557;
d = 8.47 [s, 3J(119SnA1H) = 34.8 Hz, 1H, H4], 6.82 (s, 2H, H1), 6.86–
m
(NAH), 3304–3146;
m(C@N), 1642; m(CAS), 1031;
m
m
(SnAO), 520;
m
(SnAN), 461. 1H NMR (DMSO-d6):
3
4
3
6.88 (dd, JHH = 7.9, JHH = 1.9 Hz, 2H, H8,10), 6.55 (t, JHH = 7.8 Hz,
1H, H9), 3.69 (s, 3H, H11), 0.70 [s, 3J(119SnA1H) = 80.0 Hz, 6H, SnCH3].
13C NMR (DMSO-d6): d = 5.51 (CMe), 55.54 (C11), 115.21 (C5), 115.31
(C8), 117.29 (C9), 125.21 (C10), 150.82 (C4), 155.96 (C6), 157.61 (C7),
167.58 (C2). 119Sn{1H} NMR (DMSO-d6): d = ꢀ144.4.
2. Experimental
2.1. Materials and methods
All starting materials were purchased from Merck while diphe-
nyltin dichloride was supplied by Acros Company and were all
used as received. All solvents were of reagent grade and used with-
out further purification. IR spectra were obtained from a Perkin–El-
mer BX II spectrometer as KBr discs and were reported in cmꢀ1
units. The 1H, 13C and 119Sn NMR spectra were recorded with a Bru-
ker 500 MHz Avance Ultrashield spectrometer at 500.130 MHz,
125.770 MHz and 186.50 MHz, respectively, using TMS for 1H
and 13C and SnMe4 for 119Sn NMR, as references.
2.5. Synthesis of Bu2Sn(mstsc) (3)
Complex 3 was synthesized as described for 1 from Bu2SnCl2
(0.076 g, 0.25 mmol), but the solution was refluxed for 5 h. The
yellow crystals suitable for X-ray crystallography were obtained
when the mother liquor was evaporated at r.t. Yield: 0.0835 g
(49%); m.p. 128 °C; Anal. Calcd. for C17H27N3O2SSn: C, 44.84; H,
6.07; N, 9.11%. Found: C, 44.78; H, 5.92; N, 9.22%. FT-IR (KBr,

138
M. Khandani et al. / Journal of Molecular Structure 1037 (2013) 136–143
cmꢀ1):
1552;
m
(NAH), 3308–3175;
m
(C@N), 1634;
m
(CAS), 1077;
m
(CAO),
and three Gram-negative (Pseudomonas aeruginosa ATCC-13048,
Escherchia Coli ATCC-5224 and proteus ATCC-5346) bacteria. In or-
der to compare the results, Ceftizoxime (5 mg/disc), Ampicillin
(10 mg/disc), Tobramycin (10 mg/disc), Carbenicillin (100 mg/
disc), Ciprofloxacin (5 mg/disc), Nalidixic acid (30 mg/disc) and
Erythromycin (15 mg/disc) were used as standard drugs. Determi-
nation of the antibacterial activity was carried out by paper-disc
diffusion method. The compounds were dissolved in DMSO at 5
and 50 mg/mL concentration. Muller Hinton broth was used for
preparing basal media for the bioassay of the organisms. A lawn
culture from 0.5 MacFarland suspension of each strain was pre-
pared on Muller Hinton agar. Blank paper discs (6.4 mm diameter)
m
(SnAO), 547;
m
(SnAN), 460. 1H NMR (DMSO-d6): d = 8.51
[s, 3J(119SnA1H) = 35.2 Hz, 1H, H4], 6.83 (s, 2H, H1),
3
4
3
6.86–6.88 (dd, JHH = 7.8, JHH = 3.0 Hz, 2H, H8,10), 6.55 (t, JHH
7.8 Hz, 1H, H9), 3.70 (s, 3H, H11), 1.49 [m, 4H, H (SnBu2)], 1.34
=
a
3
[m, 4H, Hb(SnBu2)], 1.29 [m, 4H, H (SnBu2)], 0.78 [t, JHH = 7.3 Hz,
c
6H, Hd(SnBu2)]. 13C NMR (DMSO-d6); d = 13.49 (Cd, SnBu2), 25.75
[C , 3J(119SnA13C) = 88.9 Hz, SnBu2], 25.96 (C , SnBu2), 27.08
c
a
[Cb, 2J(119SnA13C) = 34.4 Hz, SnBu2], 25.75, 55.80 (C11), 115.34
(C5), 115.47 (C8), 117.24 (C9), 125.23 (C10), 150.72 (C4), 156.52
(C6), 157.98 (C7), 167.52 (C2). 119Sn{1H} NMR (CDCl3): d = ꢀ145.2.
were saturated with a solution of test compounds (40 lL) and
2.6. X-ray crystal structure determination
placed on the surface of the agar plates. On one paper disc only
DMSO was poured as a control. The plates were incubated at
37 °C for 24 h. The inhibition zone diameters around each disc
were measured in mm.
The X-ray diffraction measurements were made on a STOE
IPDS-IIT diffractometer with graphite monochromated Mo Ka radi-
ation. Cell constants and an orientation matrix for data collection
were obtained by least-squares refinement of the diffraction data
from 3656 unique reflections for 2 and 3507 for 3. Data were col-
lected at a temperature of 298(2) K and were integrated using the
Stoe X-AREA [21] software package. A numerical absorption cor-
rection was applied using X-RED [22] and X-SHAPE [23] software.
The data were corrected for Lorentz and Polarizing effects. The
structures were solved by direct methods and subsequent differ-
ence Fourier maps and then refined on F2 by a full-matrix least-
squares procedure using anisotropic displacement parameters
[24]. Atomic factors are from International Tables for X-ray Crystal-
lography [25]. All refinements were performed using the X-STEP32
crystallographic software package [26]. Details of data collection,
structure solution and refinements are summarized in Table 1.
2.8. Anti-tumor activity
Antiprolifration behavior of ligand and synthesized complexes
in vitro was studied against Jurkat (human acute lymphoblastic
leukemia) cell line. Cells were grown in 50 mL plastic culture flask
(SPL, Korea) in RPMI 1640 (Biosera, UK) supplemented with 10%
heat-inactivated fetal calf serum (Biosera, UK), 100 lg/mL of strep-
tomycin and 100 IU/mL of penicillin (Gibco, US) and incubated at
37 °C in a 5% CO2 incubator.
2.8.1. WST-1 cytotoxicity assay
The assay was based on the cleavage of the tetrazolium salt
WST-1 producing a soluble formazan salt (Roche, Germany). 96
well tissue culture micro plates (SPL, Korea) were seeded with
2.7. Antibacterial tests
90 lL medium containing cells in suspension. Different concentra-
The in vitro antibacterial activity of ligand and its corresponding
organotin(IV) complexes was investigated against the standard
strains of one Gram-positive (Staphylococcus aureus ATCC-6538)
tions of synthesized compounds (1.26 mg/mL, 0.63 mg/mL,
0.3150 mg/mL, 0.1575 mg/mL, 0.0787 mg/mL, 0.039 mg/mL,
0.019 mg/mL and 0.0098 mg/mL) in DMSO and Tween20 were
Table 1
Crystal data and structure refinement data for 2 and 3.
2
3
Empirical formula
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system, space group
a (Å)
C
11H15N3O2SSn
C17H27N3O2SSn
456.20
298(2)
0.71073
Trigonal, R-3
33.923(2)
33.923(2)
9.0112(6)
90
90
120
8980.5(10)
18, 1.518
1.399
372.04
298(2)
0.71073
Triclinic, Pı
¯
7.5048(9)
9.4712(12)
10.4093(12)
96.307(10)
106.784(10)
100.379(10)
686.41(14)
2, 1.800
b (Å)
c (Å)
a
(°)
b (°)
c
(°)
Volume (Å3)
Z, Calculated density (Mg/m3)
Absorption coefficient (mmꢀ1
F(000)
)
2.011
736
4176
Crystal size (mm)
Theta range for data collection (deg.)
Limiting indices
0.40 ꢁ 0.20 ꢁ 0.15
0.25 ꢁ 0.20 ꢁ 0.10
2.07–26.00
2.08–24.99
ꢀ9 6 h 6 9
ꢀ26 6 h 6 40
ꢀ11 6 k 6 11
ꢀ39 6 k 6 19
ꢀ12 6 l 6 12
ꢀ9 6 l 6 10
Reflections collected/unique
Completeness to h = 29.18
Absorption correction
5735/2687 [R(int) = 0.1115]
99.4%
6443/3507 [R(int) = 0.0418]
99.6
Numerical
Numerical
Max. and min. transmission
Refinement method
0.742 and 0.621
Full-matrix least-squares on F2
2687/0/166
0.871 and 0.720
Full-matrix least-squares on F2
3507/6/217
Data/restraints/parameters
Goodness-of-fit on F2
1.053
1.044
Final R indices [I > 2sigma(I)]
R indices (all data)
R1 = 0.0634, wR2 = 0.1685
R1 = 0.0657, wR2 = 0.1710
1.034 and ꢀ1.437
R1 = 0.0898, wR2 = 0.2134
R1 = 0.1243, wR2 = 0.2321
1.218 and ꢀ1.127
Largest diff. peak and hole (e Å3)

M. Khandani et al. / Journal of Molecular Structure 1037 (2013) 136–143
139
added to the cells in 10
lL volumes in triplicates. After 48 hrs of
3.2. IR Spectra
incubation in a CO2 incubator (37 °C), 10
lL of WST-1 was added
to the test wells and the plate was further incubated in 37 °C for
4 h. The absorbance was then determined in 490 nm and a refer-
ence wavelength of 630 nm by an ELISA spectrophotometer
(Awareness, USA). All experiments were repeated three times
and each experimental condition was repeated in triplicate wells
in each experiment. Besides the wells with our synthesized compo-
nents dissolved in solvent (DMSO and Tween20), the cells were
also cultured in two other conditions in separate wells: (i) Cells
plus the different concentrations of the solvent alone, equal to
the concentrations used for dissolving the synthesized compo-
nents; (ii) Cells alone, with no other additive rather than the cul-
ture media. The viability percentage of the cells was firstly
calculated for these two conditions to determine the concentra-
tions of the solvents with no significant effects on cell survival.
Information from the synthesized components was included in
the final analysis only for the wells in which the concentration of
the solvent did not exceed these values.
The bands attributed to
m
(NNAH) and
m
(OAH) in the free ligand
disappear on complex formation and points to double deprotona-
tion of the ligand during coordination. The (C@N) band at
1621 cmꢀ1 for ligand is shifted in the spectra of complexes, indicat-
ing coordination of the azomethine nitrogen to the tin. The (CAO)
band of the ligand shifts to the higher wavenumber in the spectra
of complexes [29]. This observation indicates that the phenolic
oxygen atom is involved in coordination to the tin atom. The band
at 1120 cmꢀ1 in the spectrum of ligand assigned to the thiocarbon-
yl group is shifted to a lower energy after complexation, indicating
coordination via the thiolate sulfur. The appearance of new bands
in the IR spectra of the complexes at 453–461 and 520–597 as-
m
m
signed to
of nitrogen and oxygen to the tin atom [9,10,29–31]. Presence of
both s(SnAC) and as(SnAC) in the IR spectrum of 2 is consistent
m(SnAN) and m(SnAO), respectively, supports the bonding
m
m
with a nonlinear MeASnAMe configuration [9].
3.3. NMR spectra
In the 1H NMR spectra of complexes the absence of both pheno-
lic and hydrazinic signals suggests deprotonation and coordination
of dianionic ligand to tin. The two NH2 protons, which appear at
7.80 and 8.10 ppm in the spectrum of free thiosemicarbazone shift
upfield and become chemically equivalent in complexes. It is prob-
ably due to the reduction in CAN bond order indicated by the X-ray
study and to the rupture of the hydrogen bond interaction involv-
ing these protons when the conformation of the ligand is modified
upon complexation [32,33]. In the 1H NMR spectra of complexes
appearance of satellites around azomethine proton signal (Fig. 2)
due to 3J(119SnA1H) coupling indicates the imine nitrogen atom
is coordinated to tin(IV). The 1H NMR spectrum of 2 shows a singlet
at 0.77 ppm for SnMe2 protons accompanied by satellites because
of 119SnA1H coupling (Fig. 2). Substitution of this coupling constant
in the Lockhart–Manders equation [34] gives a value 130.84° for
the MeASnAMe angle.
3. Results and discussion
3.1. Synthesis
3-Methoxysalicylaldehyde thiosemicarbazone was prepared by
reaction of 3-methoxysalicylaldehyde and thiosemicarbazide
according to the modified procedure described in the literature
[20]. On the basis of previous reports [20,27,28] this compound
is in thione tautomeric form both in solid phase and in solution
(Fig. 1). The new complexes 1–3 were prepared by reaction of
R2SnCl2 (R = Ph, Me and Bu) with this thiosemicarbazone ligand
in methanol in presence of triethylamine as a base to force the
deprotonation of the ligand. The synthesized complexes were
characterized by IR and 1H, 13C and 119Sn NMR spectroscopy. The
structures of 2 and 3 have been determined by X-ray diffraction.
Fig. 2. 1H NMR spectrum of 2.

140
M. Khandani et al. / Journal of Molecular Structure 1037 (2013) 136–143
shown in Figs. 5 and 6. Selected bond distances and angles are gi-
ven in Table 2. It is to be noted that carbon atoms of butyl groups in
3, have a high thermal parameter due to data collection in room
temperature. We tried refining these atoms in two positions with
reduced occupancy but while this model converged satisfactorily,
there was no decreasing in R value and therefore we consider that
our refinement is the best that can be achieved and should be
reported.
In the crystal structure of 2, adjacent molecules are linked to
each other from one side by head-to-tail dimeric NAHꢂ ꢂ ꢂN classical
hydrogen bonds and from the other side by the weak intermolec-
ular CAHꢂ ꢂ ꢂO non-classical hydrogen bonds (Fig. 5, Table 3). In 3,
additionally, there are two other types of intermolecular hydrogen
bonds, N3–H3Bꢂ ꢂ ꢂO1 and N3–H3Bꢂ ꢂ ꢂO2, which formed a five-mem-
bered ring. Therefore one molecule of 3 involves in six hydrogen
bonds (Fig. 6). In this molecule the C1AH1Bꢂ ꢂ ꢂO1 hydrogen bond
further stabilized the crystal packing. Hydrogen bond distances
and angles are listed in Table 3.
Fig. 3. Crystal structure of 2. Thermal ellipsoids are shown in 50% probability level.
Thiosemicarbazone acts as a tridentate dianionic ligand and
coordinates to tin through phenolic oxygen, the azomethine nitro-
gen and thiolate sulfur atoms. The coordination sphere is com-
pleted by two carbon atoms of organic groups. The coordinated
part of the ligand is made of six and five membered chelate rings.
None of these chelate rings is planar as torsion angles are
SnAO2AC9AC8 (25.0°), SnAS1AC11AN2 (ꢀ5.5°), SnAN1AC10AC8
(ꢀ7.1°) and SnAN1AN2AC11 (9.6°) in 2 and SnAO2AC1AC7
(ꢀ32.1°), SnAS1AC9AN2 (ꢀ5.0°), SnAN1AC8AC7 (5.3°) and
SnAN1AN2AC9 (8.8°) for 3. To quantify the extent of distortion
from either ideal square pyramid (SP) or trigonal bipyramid
(TBP), the index of trigonality,
s, defined by Reedijk and coworkers
[40] have been found. The value is 0.26 for 2 and 0.42 for 3, there-
s
fore the metal coordination geometry for both complexes is de-
scribed as distorted square pyramid (t = 0.0 and 1.0 for SP or TBP
geometries, respectively). In the geometry of 2, O2, S1, N1 and C1
atoms are at the square base position and C2 is on the apex and
in 3 C10, C14, O2 and S1 are in square plane with N1 occupying
the apical position.
The crystal structure of H2mstsc has been reported by Zhao
et al. [27] and Vrdoljak et al. [28]. The bond lengths and angles
in complexes 2 and 3 have changed in comparison with the free li-
gand. The C11AS1 bond length in 2 has increased from 1.688(4) Å
in ligand [27] to 1.724(7) Å in complex whereas C11AN2 has
decreased from 1.342(5) Å to 1.303(8) Å. Also for 3 the C9AS1 bond
length increases to 1.717(12) Å and C9AN2 decreases to
1.316(13) Å. These changes indicate thiolization and charge delo-
calization in the thiosemicarbazone moiety upon deprotonation
and coordination. During the formation of the complex, a confor-
mational change of the ligand from trans to cis configuration (refer
to S1 and N1) occurs. Upon coordination also a 180° rotation of
phenyl ring occurs thereby allows the phenolic oxygen atom to
form a six membered chelate ring with the metal and imine nitro-
gen. The lengthening of azomethine bond from 1.271(5) Å in ligand
[27] to 1.306(8) Å in 2 and 1.289(12) in 3 is a consequence of
involvement of imine nitrogen in coordination to tin atom.
The SnAN and SnAO bond lengths in both complexes are like to
the sum of the covalent radii of SnAN (2.15 Å) and SnAO (2.10 Å)
[41,42], and this indicates the strong covalent bond between tin
and phenolic oxygen and imine nitrogen. The SnAS distance is
2.544 Å in 2 and 2.564 in 3, which is close to the sum of the covalent
radii of tin and sulfur 2.42 Å [43], but significantly below the sum of
the van der waals radii of these atoms (4.0 Å) [44], indicating a cova-
lent SnAS bond. To get an idea about the bond distances around Sn
atoms in these compounds, a simple survey in the Cambridge Struc-
tural Database (CSD) search was carried out [45]. The results show
there is 32 hits with five coordinated Sn(C)2(O)(S)(N) fragment in
which 9 structures include Sn(C)2(O)(NAN@C(NH2)AS) fragment
Fig. 4. Crystal structure of 3. Thermal ellipsoids are shown in 30% probability level.
The 13C NMR spectra of complexes show significant down-field
shifts compared with the free ligand, however, C2 is strongly
shielded by complexation. This shielding effect is a consequence
of electron redistribution and aminothione-iminothiol evolution
of the thioamide group reinforcing C(2)AN(3) bond order and out-
weighing the deshielding inductive effect of the SnAS bond [33].
The total effect at C(2) is superposition of a coordination induced
effect and the formation of an imine instead of a thiocarbonyl bond
[28].
The 119Sn{1H}NMR spectra of all complexes show one sharp sin-
glet significantly at lower chemical shift than that of the original
Ph2SnCl2 (ꢀ32 ppm), Me2SnCl2 (+137 ppm) and Bu2SnCl2
(+123 ppm) [35]. This large upfield shift is because of the increas-
ing in the coordination number of tin. On the basis of the chemical
shift ranges proposed empirically for organotin(IV) derivatives
[30,36–39], the coordination number of tin is five for all
complexes.
3.4. X-ray studies
Figs. 3 and 4 show the molecular structure of 2 and 3 with num-
bered atoms, respectively. A representation of hydrogen bonds are

M. Khandani et al. / Journal of Molecular Structure 1037 (2013) 136–143
141
Fig. 5. A representation of the unit cell and hydrogen bondings (all dashed lines) for 2.
Fig. 6. A representation of hydrogen bonding (dashed lines) in 3.
[46–50]. In these complexes, the SnAN, SnAS, SnAC and SnAO bond
distances are in the range of 2.175–2.371, 2.456–2.537, 2.098–2.137
and 2.061–2.154 Å, respectively. So, for both compounds studied
here, bond distances are in normal ranges.
In complex 2, the slight difference between the C2ASn1AC1
angle and X-ray data, 126.4(3)°, and the empirical estimation in
solution (130.8°) may be related to removing the crystal network
pressure in solution and also interaction of coordinating DMSO
with tin.
of the organic groups bound to tin. Since permeability across the
bacterial cell wall is necessary for the effectiveness of the biocide
compounds, therefore each factor which facilitates microorganism
membrane crossing may enhance the activity. The highest activity
of methyltin derivative can be explained on the basis of low molec-
ular weight causes its high diffusion potency. It is remarkable that
the bacteria of the genus Pseudomonas are a group of resistant
microorganism that many standard drugs were found to have no
activity against it [55,56]. Therefore it is interesting that P. aerugin-
osa was inhibited by 2. It is apparent that in more cases toxicity
towards S. aureus (as Gram-positive bacteria) is more than
Gram(ꢀ) strains. The reason is the difference in the structures of
the cell walls. The walls of Gram(ꢀ) cells are more complex than
those of Gram(+) cells. Lipopolysacharides form an outer lipid
membrane and contribute to the complex antigenic specificity of
Gram(ꢀ) cells. A mechanism postulated for action of antibacterial
compounds is deactivation of various cellular enzymes or
denaturation of one or more proteins of the cell [9,57]. It may in-
volve the formation of SnAX bonds at active biological centers
3.5. Antibacterial activity
The in vitro antibacterial activities of the ligand and its organo-
tin(IV) complexes were studied along with standard antibacterial
drugs, viz, Erythromycin, Carbenicillin, Tobramycin, Nalidixic acid,
Ampicillin, Ciprofloxacin and Ceftizoxime. The microorganisms
used in this work include S. aureus (as Gram-positive bacteria)
and E. coli, proteus and P. aeruginosa (as Gram-negative bacteria).
The results are presented in Table 4. Comparing the biological
activity of the free ligand, organotin(IV) complexes and standard
drugs, indicate that H2mstsc has no activity, while the inhibitory
effects enhance upon complexation. This enhancement may be
due to increasing the lipophilic character and efficient diffusion
of the metal complexes into bacterial cell (chelation theory)
[51–54] and also because of the intrinsic biological activity effects
of organotin moiety. The results show that dimethyltin complex
has more inhibition on microbial growth especially on P. aerugin-
osa. Generally, biological activity of organotin(IV) complexes is
influenced both by donor ligand and by the number and nature
(X = Npuric
pyrimidinic, Ocarboxylate), which, as a result, impairs
and
normal cellular processes and methabolic pathways of these
organisms [58–60]. However, permeability across the bacterial cell
wall is prior necessity for the effectiveness of the biocide com-
pounds against different microorganisms.
3.6. Antitumor activity
The in vitro cytotoxicities of the synthesized compounds against
Jurkat cells were evaluated by the standard WST-1 assay. Antitu-

142
M. Khandani et al. / Journal of Molecular Structure 1037 (2013) 136–143
Table 2
Table 4
Selected bond length (Å) and bond angles (°) for 2 and 3.
Antibacterial activity data of ligand and its organotin(IV) complexes.
Complex 2
Compound
Conc. (mg/mL) Inhibition zone (mm)
P. aeruginosa E. Coli Proteus S. aureus
Sn1AS1
Sn1AN1
Sn1AO2
Sn1AC1
Sn1AC2
C11AS1
2.5431(18)
2.245(5)
2.100(4)
2.141(7)
2.119(7)
1.724(6)
C11AN2
C11AN3
N2AN1
N1AC10
C10AC8
C9AO2
1.307(8)
1.348(8)
1.381(7)
1.306(7)
1.422(9)
1.316(7)
H2mstsc
5
50
5
50
5
50
5
50
n.a.
n.a.
n.a.
5
20
30
n.a.
n.a.
8
8
n.a.
n.a.
7
26
n.a
7
8
18
6
23
22
23
20
21
Ph2Sn(mstsc)
Me2Sn(mstsc)
Bu2Sn(mstsc)
10
16
28
15
15
10
34
20
30
40
35
20
C1ASn1AN1
C1ASn1AC2
C1ASn1AS1
O2ASn1AC1
O2ASn1AN1
N1ASn1AS1
S1ASn1AO2
S1ASn1AC2
O2ASn1AC2
135.0(2)
126.7(3)
92.3(2)
N1ASn1AC2
O2AC9AC8
98.4(2)
124.0(5)
129.4(5)
127.8(5)
115.4(5)
113.6(5)
97.1(2)
7
7
N1AC10AC8
N2AC11AS1
C11AN2AN1
C10AN1AN2
Sn1AS1AC11
Sn1AO2AC9
n.a.
n.a.
88.6(2)
Erythromycin
Carbenicillin
Tobramycin
Nalidixic acid
Ciprofloxacin
Ceftizoxime
Ampicillin
5
n.a.
82.96(17)
75.98(13)
151.02(16)
103.04(2)
99.1(3)
25
40
n.a.
n.a.
n.a.
7
n.a.
5
20
10
40
18
20
29
35
38
30
129.8(4)
n.a.
Complex 3
Sn1AS1
Sn1AN1
Sn1AO2
Sn1AC10
Sn1AC14
C9AS1
2.564(3)
2.203((8)
2.127(8)
2.086(14)
2.110(15)
1.717(12)
C9AN2
C9AN3
N2AN1
N1AC8
C7AC8
C1AO2
1.316(13)
1.351(13)
1.409(11)
1.289(12)
1.444(13)
1.324(13)
n.a. = No activity.
Table 5
IC50 values (lg/mL) for synthesized compounds.
C10ASn1AC14
C10ASn1AO2
C14ASn1AO2
C10ASn1AN1
C14ASn1AN1
O2ASn1AN1
C10ASn1AS1
C14ASn1AS1
O2ASn1AS1
130.1(7)
95.5(5)
88.1(5)
105.3(5)
124.5(5)
81.7(3)
101.4(4)
94.3(4)
155.5(2)
N1ASn1AS1
Sn1AO2AC1
Sn1AN1AC8
Sn1AN1AN2
Sn1AS1AC9
C9AN2AN1
N1AN2AC8
N1AC8AC7
76.8(2)
Compounds
IC50(lg/mL)
126.9(7)
124.0(6)
122.4(6)
96.8(4)
116.2(8)
113.5(8)
128.3(10)
H2mstsc
260
130
260
50
[SnPh2(mstsc)]
[SnMe2(mstsc)]
[SnBu2(mstsc)]
for the dialkyltin complexes increases with the length of the car-
bon chain of the alkyl ligand. The activity for the studied com-
pound is explained as: 3 > 1 > 2 = H2mstsc.
Table 3
Hydrogen bond lengths (Å) and angles (°) for 2 and 3.
4. Conclusion
Com- DAH–A
plex
d(DAH) d(Hꢂ ꢂ ꢂA) d(Dꢂ ꢂ ꢂA) DAHꢂ ꢂ ꢂA Symmetry code
On the basis of spectral and structural investigations, the thio-
semicarbazone is coordinated to tin as dianionic tridentate via
phenolic oxygen, the azomethine nitrogen and thiolate sulfur
atoms. Coordination geometry for dimethyl and dibutyltin com-
plexes is described as distorted square pyramid. On the basis of
119Sn NMR data, coordination number of tin retains five in solution.
The synthesized organotin complexes are evaluated in inhibiting
both Gram-positive (S. aureus) and Gram-negative (E. coli, proteus
and P. aeruginosa) bacterial species and dimethyl complex exhibits
more inhibitory effect. The in vitro cytotoxicities of the synthesized
compounds against Jurkat cells decreases in the order
3 > 1 > 2 = H2mstsc.
2
N3AH3Aꢂ ꢂ ꢂN2 0.86
2.220
2.590
3.070(8) 167
3.343(9) 135
1 ꢀ x, 1 ꢀ y, 1 ꢀ z
1 ꢀ x, ꢀy, 2 ꢀ z
C1AH1Bꢂ ꢂ ꢂO1 0.96
3
N3AH3Dꢂ ꢂ ꢂN2 0.86
N3AH3Eꢂ ꢂ ꢂO1 0.86
2.170
2.480
3.023(13) 171
2.884(15) 110
1 ꢀ x, ꢀy, 1 ꢀ z
1/3 + x ꢀ y, ꢀ1/
3 + x, 2/3 ꢀ z
1/3 + x ꢀ y, ꢀ1/
3 + x, 2/3 ꢀ z
2/3 ꢀ x, 1/3 ꢀ y,
4/3 ꢀ z
N3AH3Eꢂ ꢂ ꢂO2 0.86
C3AH3Aꢂ ꢂ ꢂO1 0.96
C8AH8Aꢂ ꢂ ꢂO1 0.93
2.250
2.570
2.490
3.068(17) 160
3.287(17) 131
3.337(15) 152
2/3 ꢀ x + y, 1/
3 ꢀ x, 1/3 + z
mor potency of the compounds were calculated by curves obtained
for each compound and Viability percent was calculated from the
following equation, and then IC50 values were mathematically
interpolated:
Supplementary material
CCDC 839364 and 859450 contain the supplementary crystallo-
graphic data for 2 and 3, respectively. These data can be obtained
free of charge via http://www.ccdc.cam.ac.uk/conts/retriev-
ing.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.
%cytotoxicity ¼ ½ODðcellÞ ꢀ ODðtestÞ=ODðcellÞꢃ ꢁ 100
where OD(Cell) is the optical density of Jurkat cells and OD(test) is
the optical density of the solutions with different concentrations of
synthesized compounds in DMSO and Tween20 and Jurkat cells.
Table 5 shows 50% inhibitory concentration (IC50) against cancer
cell line for synthesized compounds.
Acknowledgments
Although the mechanism of this antiproliferative activity is not
well established, it has been suggested that organotin(IV)
compounds wield antiproliferative effects through binding to thiol
groups of the proteins, hence differ from the behavior of several
cytotoxic complexes of other metals, e.g. Pt, which interacts with
DNA [61–63]. Also, based on the observation, antitumor activity
Support of this work by Shahid Chamran University, Ahvaz,
Iran; Shiraz Institute for Cancer Research, Shiraz University of
Medical Sciences, Shiraz, Iran; Science and Research Branch, Isla-
mic Azad University, Ahvaz, Iran and Shahid Beheshti University,
Tehran, Iran is gratefully acknowledged.

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