Homobimetallic organotin(IV) complexes with hexadentate Schiff base: Synthesis, crystal structure and antimicrobial studies

Article abstract of DOI:10.1016/j.jorganchem.2014.02.010

This article describes the synthesis of four new homobimetallic organotin(IV) complexes: [Et₂Sn]₂L (1), [Bu ₂Sn]₂L (2), [Oct₂Sn]₂L (3) and [BuClSn]₂L (4) (H₄L = N¹′,N ⁶′-bis(5-bromo-2-hydroxybenzylidene)adipodihydrazide) and their structural elucidation by means of elemental analysis, mass spectroscopy, FT-IR, NMR (¹H, ¹³C, ¹¹⁹Sn) and single crystal X-ray analysis. Spectroscopic studies indicate coordination of hexadentate ligand to the diorganotin(IV) moieties via ONO-ONO donor sites and pentacoordinated tin centers. Single crystal X-ray analysis of (1) and (2) revealed homobimetallic nature of complexes with each Sn atom in a distorted square pyramidal coordination geometry. Packing diagrams suggest the seminal role of Sna?N and Bra?π interactions in generating supramolecular assembly. The synthesized compounds were screened for their antimicrobial activity and cytotoxicity. Compound (2) exhibit highest activity against several pathogenic microbes.

Full text of DOI:10.1016/j.jorganchem.2014.02.010

Journal of Organometallic Chemistry 759 (2014) 19e26
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Homobimetallic organotin(IV) complexes with hexadentate Schiff
base: Synthesis, crystal structure and antimicrobial studies
Shaukat Shujah , Zia-ur-Rehman , Niaz Muhammad , Afzal Shah , Saqib Ali ,**,
a
,
b
c
b
b
*
d
e
Auke Meetsma , Zahid Hussain
a
Department of Chemistry, Kohat University of Science & Technology, Kohat 26000, Pakistan
Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan
Department of Chemistry, Abdul Wali Khan University, Mardan, Pakistan
b
c
d
Crystal Structure Center, Chemical Physics, Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, NL-9747 AG Groningen,
The Netherlands
e
Institute of Industrial Biotechnology, G.C. University, Lahore, Pakistan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 October 2013
Received in revised form
2 2
This article describes the synthesis of four new homobimetallic organotin(IV) complexes: [Et Sn] L (1),
1
0
6
0
[
Bu
2
Sn]
2
L (2), [Oct
2
Sn]
2
L (3) and [BuClSn]
2
L (4) (H
4
L ¼ N ,N -bis(5-bromo-2-hydroxybenzylidene)adi-
podihydrazide) and their structural elucidation by means of elemental analysis, mass spectroscopy, FT-IR,
NMR ( H, C,
24 January 2014
1
13
119
Sn) and single crystal X-ray analysis. Spectroscopic studies indicate coordination of
Accepted 18 February 2014
hexadentate ligand to the diorganotin(IV) moieties via ONOeONO donor sites and pentacoordinated tin
centers. Single crystal X-ray analysis of (1) and (2) revealed homobimetallic nature of complexes with
each Sn atom in a distorted square pyramidal coordination geometry. Packing diagrams suggest the
Keywords:
Homobimetallic
Pentacoordinated diorganotin(IV)
Supramolecular
Hexadentate Schiff base
Biological activity
seminal role of Sn/N and Br/
p interactions in generating supramolecular assembly. The synthesized
compounds were screened for their antimicrobial activity and cytotoxicity. Compound (2) exhibit highest
activity against several pathogenic microbes.
Ó 2014 Elsevier B.V. All rights reserved.
1. Introduction
hydrogen bonding, hydrophobic, hydrophilic effects, electrostatic
and pep interactions etc. [10,11].
The study of organotin(IV) complexes of Schiff bases has been a
subject of interest mainly due to their wide applications in various
fields like catalysis, biotechnology, analytical and medicinal
chemistry [1e6]. Several organotin(IV) hydrazones have been
investigated for their structural diversity [7,8]. The tin atom in these
complexes is usually pentacoordinate with a trigonal bipyramidal
or square pyramidal geometry and can act as a Lewis acid. The
coordination number can be increased by addition of molecules
with donor atoms and the geometry around tin changes to
pentagonal bipyramidal [9]. Moreover, supramolecular architec-
tures can be achieved through self-assembly of molecules by
The metal complexes of diacylhydrazones exhibit pronounced
biological and pharmaceutical activities as antitumor, antimicro-
bial, antituberculosis and antimalarial agents [12e17]. The presence
of two coordinating units connected by hydrocarbon linkers with
varying degrees of flexibility in the ligand may yield supramolec-
ular architectures such as double helices, grids, racks or coordina-
tion polymers [18]. However, few studies have been reported for
the synthesis of bis-diorganotin(IV) complexes of diacylhydrazones
with double set of ONO donor atoms [19]. The diacylhydrazones can
either act as monobasic bis-bidentate, monobasic bis-tridentate,
dibasic bis-tridentate chelators or they may form polymeric chain
[20]. In continuation with our studies on diorganotin(IV) complexes
derived from ONO donor ligands [21,22], and triggered by the need
for potent antimicrobial agents to mitigate or eliminate the in-
fections, we report herein the synthesis, spectroscopic character-
ization and antimicrobial activities of four new centrosymmetric
*
Corresponding author. Tel.: þ92 0333 5203621.
** Corresponding author. Tel.: þ92 5190642208; fax: þ92 51 2873869.
1
0
6
0
homobimetallic organotin(IV) derivatives of N ,N -Bis(5-bromo-
2-hydroxybenzylidene)adipodihydrazide, potential tetrabasic
E-mail addresses: shaukat.shujah@yahoo.com (S. Shujah), drsa54@yahoo.com
(
S. Ali).
a
http://dx.doi.org/10.1016/j.jorganchem.2014.02.010
022-328X/Ó 2014 Elsevier B.V. All rights reserved.
0

20
S. Shujah et al. / Journal of Organometallic Chemistry 759 (2014) 19e26
hexadentate ligand with ONOeONO donor atoms. The single
crystal X-ray structure and intermolecular interactions generating
supramolecular architecture for complex 1 and 2 have also been
discussed.
3
further stirred for 5 h. The white precipitates of Et NHCl formed
during the reaction were filtered. The filtrate was concentrated
by rotary evaporator under reduced pressure to obtain yellow
solid. The product was recrystallized from chloroform n-hexane
(
4:1) mixture (Scheme 2a).
Yield 78%. mp 194e196 C. Anal. Calc. for C28H36Br N O Sn
ꢁ
2
. Experimental
2 4 4 2
(
M ¼ 890): C, 37.79; H, 4.08; N, 6.30 Found: C, 37.77; H, 4.10; N,
þ
2.1. Chemicals and instrumentations
6.32% EI-MS, m/z (%): [(C
H
8 4
BrN
2
O
2
)
2
C
4
H
8
Sn
2
(C
2
H
5
)
3
]
861(100.0),
þ
þ
[(C
8
H
4
BrN
2
O
2
)Sn(C
2
H
5
)
2
]
417(6.3), [(C
8
H
4
BrN
2
O
2
)Sn(C
2
H
5
)]
þ
þ
þ
Organotin(IV) dichlorides, dioctyltin(IV) oxide, butyltin(IV)
388(6.9), [(C
2
H
5
)
2
Sn] 178 (3.1), [C
(C]N), 1079
2
H
5
Sn] 149(5.4), [Sn] 120(7.1)
ꢀ1
chloridedihydroxide,
adipic
hydrazide
and
5-bromo-2-
IR (cm ): 1609
n
n
(NeN), 569
n
(SneO), 460
n
(SneN),
1
3
119
1
hydroxybenzaldehyde were procured from Aldrich and the
organic solvents used were of Merck, Germany. These solvents
were freshly dried using standard procedures [23]. The melting
points were recorded on an electrothermal melting point appa-
ratus, model MP-D Mitamura Rieken Kogyo (Japan) by using
capillary tubes and are uncorrected. The infrared (IR) spectra
were recorded as neat liquids, using NaCl cells or as KBr pellets
for solids on a Bio-Rad Excaliber FT-IR, model FTS 300 MX spec-
H NMR (ppm): 8.49 (s, 2H, CH]N, J( Sne H) ¼ 41 Hz), 2.34 (bs,
3
4H, 2CH
2
), 1.72 (bs, 4H, 2CH
2
), 6. 64 (d, 2H, AreH, JHeH ¼ 9.0), 7.32
eSnEt,
HeH ¼ 7.5) C NMR (ppm):
159.3 (CH]N), 176.5 (NCO), 34.2, 26.1 (eCH CH ), 166.0, 137.4,
135.3, 123.5, 118.0, 107.7 (AreC), 14.2 (C eSnEt, J[
3
(dd, 2H, AreH, JHeH ¼ 9.0), 7.18 (s, 2H, AreH), 1.42 (q, 8H, H
a
3
3
13
J
HeH ¼ 7.2), 1.24 (t, 12H, H
b
eSnEt, J
2
2
1
119/117
a
13
Sne
Sn
1
3
2
119
119
C] ¼ 614, 587 Hz), 9.2 (C
b
eSnEt, J[ Sne C] ¼ 42 Hz),
NMR:
d
(ppm) ¼ ꢀ192.5.
ꢀ
1
trophotometer (USA) in the frequency range of 4000e400 cm
.
1
13
119
1
0
6
0
Multinuclear NMR ( H, C, and Sn) spectra were recorded on a
Bruker ARX 300 MHz-FT-NMR and a Bruker 400 MHz-FT-NMR
2.2.3. Bis[di-n-butyltin(IV)][N ,N -bis(5-bromo-2-oxidobenzylidene)
adipodihydrazide] (2)
spectrometers Switzerland using CDCl
3
as an internal reference.
Compound 2 was prepared in the same way as 1, using
1
0
6
0
Chemical shifts ( ) are given in ppm and coupling constants (J) are
d
following precursors quantities: N ,N -bis(5-bromo-2-hydroxy
benzylidene)adipodihydrazide 0.81 g (1.5 mmol), dibutyltin(IV)
dichloride 0.91 g (3.0 mmol) and triethylamine 0.84 mL (6.0 mmol)
were reacted in a 1:2:4 ratio. The solid product was recrystallized
1
given in Hz. The multiplicities of signals in H NMR are given with
chemical shifts; (s ¼ singlet, d ¼ doublet, t ¼ triplet, q ¼ quartet,
m ¼ multiplet, bs ¼ broad signal). The mass spectra were recor-
ded on a MAT-311A Finnigan (Germany). The m/z values were
evaluated assuming that H ¼ 1, C ¼ 12, N ¼ 14, O ¼ 16, Cl ¼ 35
and Sn ¼ 120.
from a chloroform n-hexane (4:1) mixture.
ꢁ
Yield 78%. mp 99e101 C. Anal. Calc. for C36
2
H54Br N
4
O
4
Sn
2
(M ¼ 1004): C, 43.06; H, 5.42; N, 5.58 Found: C, 43.17; H, 5.20; N,
þ
The X-ray diffraction data were collected on a Bruker SMART
APEX CCD diffractometer, equipped with a 4 K CCD detector. Data
integration and global cell refinement was performed with the
program SAINT. The program suite SAINTPLUS was used for
space group determination (XPREP). The structure was solved by
Patterson method; extension of the model was accomplished by
direct method and applied to different structure factors using
the program DIRDIF. All refinement calculations and graphics
were performed with the program PLUTO and PLATON package
5.61% EI-MS, m/z (%): [(C
8
H
4
BrN
2
]
O
2
)
2
C
4
H
8
Sn
2
(C
4
H
9
)
3
]
945(100.0),
BrN
þ
[(C
Sn(C
[(C
8
H
4
BrN
2
O
2
)CNC
4
H
8
Sn(C
4
H
9
)
2
555(23.5),
[(C
H
8 4
2 2
O )
þ
þ
4
9
H )
2
]
473(3.1),
[(C
8
H
4
BrN
H
2
O
2
)Sn(C
4
H
9
)]
416(6.1),
þ
þ
þ
8
H
4
BrN
2
O
2
)Sn] 281(8.0), [(C
4
9
)
2
Sn] 234(4.3), [C
4
9
H Sn]
þ
þ
þ
177(18.4), [Sn] 120(7.0), [C
6
H
5
]
77(3.4), [C
4
H
9
]
57(74.5) IR
ꢀ
1
1
(cm ): 1609
n
(C]N), 1078
n
(NeN), 590
n
1
(SneO), 453
n
(SneN), H
3
119
NMR (ppm): 8.48 (s, 2H, CH]N, J( Sne H) ¼ 41 Hz), 2.35 (bs, 4H,
3
2CH
2H, AreH, JHeH ¼ 9.0), 7.20 (s, 2H, AreH), 1.57e1.67 (m, 8H, H
SnBu), 1.44e1.49 (m, 8H, H eSnBu), 1.28e1.40 (m, 8H, H eSnBu),
eSnBu, JHeH ¼ 7.2) C NMR (ppm): 159.2 (CH]N),
2
), 1.72 (bs, 4H, 2CH
2
), 6. 65 (d, 2H, AreH, JHeH ¼ 9.0), 7.35 (dd,
3
a
e
[
24e28].
b
g
3
13
0
.88 (t, 12H, H
d
2
2
.2. Synthesis
176.3 (NCO), 34.2, 25.8 (eCH
2
CH
2
), 165.8, 137.4, 135.3, 123.6, 118.0,
1
119/117
13
1
07.6 (AreC), 22.1 (C
a
eSnBu, J[
Sne C] ¼ 599, 574 Hz), 26.8
1
0
6
0
2
119/117
13
3 119/117
.2.1. Synthesis of N ,N -bis(5-bromo-2-hydroxybenzylidene)
L)
(C
b
eSnBu, J[
Sne C] ¼ 34 Hz), 26.4 (C
g
eSnBu, J[
Sne
1
3
119
adipodihydrazide (H
4
C] ¼ 86 Hz), 13.4 (C
d
eSnBu), Sn NMR:
d
(ppm) ¼ ꢀ190.3.
1
0
6
0
The synthesis of N ,N -bis(5-bromo-2-hydroxybenzylidene)
adipodihydrazide was carried out by a reported method [29]. To a
solution (25 mL) of adipic dihydrazide, 1.0 g (5.74 mmol) in ethanol
was added a solution (25 mL) of 5-bromo-2-hydroxybenzaldehyde
2
.47 g (11.48 mmol) in ethanol. The mixture was stirred and
refluxed for 2 h. A white solid product was obtained (Scheme 1).
Yield 77%. Anal. Calc. for C20
(M ¼ 538): C, 44.47; H,
.73; N, 10.37 Found: C, 44.50; H, 3.70; N, 10.40%. EI-MS, m/z (%):
2 4 4
H20Br N O
3
þ
þ
[C
20
H
20Br
2
N
4
O
4
]
538(20.7), [C13
H
14BrN
2
O
3
]
325(81.4), [C
8
H
6
Br
þ
þ
þ
N
2
O
2
]
241(9.1), [C
7
H
4
BrNO] 197(100.0), [C
7
4
H NO] 118(4.5),
þ
þ
þ
5
H ] 77(16.7).
[C
7
H
3
BrN] 180 (3.8), [C
6
H
4
BrO] 171(18.7), [C
6
1
0
6
0
2
.2.2. Bis[diethyltin(IV)][N ,N -bis(5-bromo-2-oxidobenzylidene)
Sn) L (1)
The triethylammonium salt of ligand (H
adipodihydrazide](Et
2
2
4
L) was synthesized
by reacting N ,N -bis(5-bromo-2-hydroxybenzylidene)adipodi-
hydrazide 0.81 (1.5 mmol) and triethylamine 0.84 mL
6.0 mmol) in dry toluene. The mixture was stirred for 15 min at
room temperature and diethyltin(IV) dichloride 0.74
3.0 mmol) was added. The solution turned yellow and was
1
0
6
0
g
(
g
Scheme 1. Synthesis of N10,N60-bis(5-bromo-2-hydroxybenzylidene)adipodihydrazide
(H L).
(
4

S. Shujah et al. / Journal of Organometallic Chemistry 759 (2014) 19e26
21
Scheme 2. Synthesis of bis[diorganotin(IV)] and bis[butylchlorotin(IV)] derivatives (a, b). Numbering scheme of alkyl groups bonded to tin atom in bis[dialkyltin(IV)] derivatives of
H L (c).
4
1
0
6
0
2
.2.4. Bis[di-n-octyltin(IV)][N ,N -bis(5-bromo-2-
product was recrystallized from a chloroform and n-hexane (4:1)
oxidobenzylidene)adipodihydrazide](3)
mixture.
1
0
6
0
ꢁ
Compound 3 was prepared by refluxing N ,N -bis(5-bromo-2-
hydroxybenzylidene)adipodihydrazide 0.81 g (1.5 mmol) and dio-
ctyltin(IV) oxide 1.09 g (3.0 mmol) in 100 mL dry toluene in 1:2
ratio. The water formed during the reaction was removed by Dean-
Stark apparatus. The yellow solution obtained was rotary evapo-
rated under reduced pressure. A viscous liquid product was
obtained (Scheme 2b).
Yield 70%. mp 140e143 C. Anal. Calc. for C28
H
34Br
2
Cl
2
N
4
O
4
Sn
2
(M ¼ 958): C, 35.08; H, 3.57; N, 5.84 Found: C, 35.05; H, 3.60; N,
þ
5.80% EI-MS, m/z (%): [(C
8
H
4
BrN
(C
866(9.1),
2
H
O
2
)
2
C
]
4
H
8
Sn
901
[(C
)Sn(C
BrN
2
(C
4
H
9
)
2
Cl]
þ
923(73.8),
[(C BrN
CNC Sn (C
451(7.0), [(C
[(C
8
H
4
BrN
2
O
2
)
2
C
)Cl]
4
H
8
Sn
2
4
9
)Cl
2
(32.2),
þ
8
H
4
2
O
2
)
2
C
4
H
8
Sn (C
2
4
H
9
8
H
4
BrN
)Cl]
)SnCl]
2
O
2
)
þ
þ
þ
4
H
8
4
H
9
)Cl]
533(5.6), [(C
)Sn(C
)Sn] 359(4.6), [(C
8
H
4
BrN
2
O
2
4
H
9
þ
8
H
4
BrN
2
O
2
4
H
9
)] 416(5.2), [(C
8
H
4
2
O
2
þ
þ
Yield 76%. mp viscous liquid. Anal. Calc. for C52
H
84Br
2
N
4
O
4
Sn
2
394(3.9), [(C
H
8 4
BrN
2
O
2
4
H
9
)ClSn] 212(8.5),
þ
þ
þ
ꢀ1
(
4
M ¼ 1226): C, 50.92; H, 6.90; N, 4.57 Found: C, 50.89; H, 6.87; N,
[ClSn] 155(23.4), [Sn] 120(6.7), [C
4
H
9
]
57(100.0) IR (cm ): 1609
þ
þ
(SneN) 1H NMR (ppm):
.55% EI-MS, m/z (%): [(C
8
4
H BrN
2
O
2
)CNC
4
H
8
Sn(C
BrN
8
H
17
)
2
]
667(4.8),
n
(C]N), 1072
n
(NeN), 560
n
(SneO), 451
), 1.72 (bs, 4H, 2CH
2H, AreH, JHeH ¼ 9.0), 7.41 (bs, 2H, AreH), 7.21 (s, 2H, AreH),1.68e
1.72 (m, 4H, H eSnBu), 1.43e1.50 (m, 4H, H eSnBu), 1.34e1.41 (m,
4H, H eSnBu), 0.94 (t, 6H, H
159.7 (CH]N),175.1 (NCO), 34.2, 25.6 (eCH
124.4, 118.2, 107.5 (AreC), 23.7 (C eSnBu), 27.2 (C
eSnBu), Sn NMR:
(ppm) ¼ ꢀ200.
n
þ
[
[
(
(C
C
8
H
4
BrN
2
O
2
)Sn(C
8
H
17)] 472 (4.5), [(C
8
H
4
2
O
2
)Sn] 359(3.9),
8.51 (s, 2H, CH]N), 2.37 (bs, 4H, 2CH
2
2
), 6. 81 (d,
þ
þ
þ
3
7
H
4
NOSn] 238(29.8), [Sn] 120(6.5), [C
4
H
9
]
57(100.0) IR
ꢀ
1
1
cm ): 1621
n
(C]N), 1082
n
(NeN), 578
n
1
(SneO), 466
n
(SneN) H
a
b
3
119
3
13
NMR (ppm): 8.46 (s, 2H, CH]N, J( Sne H) ¼ 41 Hz), 2.32 (bs, 4H,
g
d
eSnBu, JHeH ¼ 7.5) C NMR (ppm):
CH ), 64.7, 135.3, 132.4,
eSnBu), 26.3
3
2
2
CH
H, AreH, JHeH ¼ 9.0), 7.17 (s, 2H, AreH), 1.57e1.64 (m, 8H, H
eSnOct), 1.20e1.29 (bs, 40H, H
2
), 1.71 (bs, 4H, 2CH
2
), 6. 62 (d, 2H, AreH, JHeH ¼ 8.7), 7.30 (dd,
2
2
3
a
e
e
a
b
1
19
SnOct), 1.42e1.47 (m, 8H, H
SnOct), 0.85 (t, 12H, H
CH]N), 176.3 (NCO), 34.2, 26.1 (eCH
b
g
e
g
0
(C
g
eSnBu), 13.7 (C
d
d
3
13
0
eSnOct, JHeH ¼ 7.2) C NMR (ppm): 159.2
d
(
2
CH
2
), 165.7, 137.4, 135.3,
2.3. Antibacterial activity
1
119/117
13
1
23.5, 118.0, 107.7 (AreC), 22.7 (C
a
eSnOct, J[
Sne C] ¼ 627,
2
119/117
13
5
J[
99 Hz), 24.7 (C
b
eSnOct, J[
Sne C] ¼ 36 Hz), 33.4 (C
g
eSnOct,
The synthesized compounds were tested for antibacterial ac-
tivity against Escherichia coli ATCC 11229, Bacillus subtilis ATCC
11774, Shigella flexneri ATCC 10782, Staphylococcus aureus ATCC
3
119/117
13
19
Sne C] ¼ 78 Hz), 29.2, 29.0, 31.8, 22.5 (C
deg
0
eSnOct), 14.1
(
C
d
eSnOct), 1 Sn NMR:
d
(ppm) ¼ ꢀ198.
25923, Pseudomonas aeruginosa ATCC 10245 and Salmonella typhi
1
0
6
0
2
.2.5. Bis[n-butylchlorotin(IV)][N ,N -bis(5-bromo-2-
ATCC 10749 using the agar well diffusion method [30]. Imipenum
was used as standard drug and 6 mm diameter wells were dug in
the media with the help of a sterile metallic borer. Eight hours old
bacterial inoculums containing approximately 10 e10 colony
forming units (CFU)/mL were spread on the surface of nutrient agar
with the help of a sterile cotton swab. The recommended
oxidobenzylidene)adipodihydrazide] (4)
Compound 4 was prepared in the same way as 3, using following
1
0
6
0
4
6
precursors quantities: N ,N -bis(5-bromo-2-hydroxybenzylidene)
adipodihydrazide 0.81 g (1.5 mmol) and butyldihydroxidetin(IV)
chloride 0.73 g (3.0 mmol) were reacted in a 1:2 ratio. The solid

22
S. Shujah et al. / Journal of Organometallic Chemistry 759 (2014) 19e26
Fig. 1. Molecular structure of compound 1, hydrogen atoms are omitted for clarity.
ꢁ
concentration of the test sample (2 mg/mL in DMSO) was intro-
duced into the respective wells. Other wells supplemented with
DMSO and reference antibacterial drug served as negative and
positive controls, respectively. The plates were incubated imme-
streak was employed. The tubes were incubated at 27e29 C for 7e
10 days and growth in the compound containing media was
determined by measuring the linear growth (in mm) and growth
inhibition with reference to the respective control.
ꢁ
diately at 37 C for 20 h. The activity was determined by measuring
the diameter of the inhibition zone (in mm), showing complete
inhibition. Growth inhibition was calculated with reference to the
positive control.
2.5. Cytotoxicity
The cytotoxicity of the compounds was studied by the Brine
shrimp lethality bioassay [31]. Brine shrimps (Artemia salina) were
hatched using brine shrimp eggs in a vessel, filled with sterile
simulated seawater (prepared using sea salt 38 g L and adjusted
to pH 8.5 using 1 M NaOH) at room temperature 22e29 C under
2.4. Antifungal activity
ꢀ1
ꢁ
The in vitro antifungal activity of synthesized compounds was
also investigated against six fungal strains [Trichophyton longifusus
ATCC 22397, Candida albicans ATCC 2192, Aspergillus flavus ATCC
constant aeration for two days. After hatching, thirty active nauplii
were drawn through a glass capillary and placed in a vial containing
4.5 mL of brine solution and a drop of yeast suspension. In each
experiment, 0.5 mL of the test solution was added to the vial and
maintained at ambient temperature for 24 h, the surviving larvae
were counted. All the experiments with different concentrations (1,
1030, Microsporum canis ATCC 9865, Fusarium solani ATCC 11712,
Candida glabrata ATCC 90030] using the agar tube dilution test [31].
Miconazole and Amphotericin B were used as standard drugs for
comparison.
Stock solutions of pure compounds (200
mg/mL) were prepared
10, 100 mg/mL) of the test substances were conducted in triplicate
in sterilized DMSO. Sabouraud dextrose agar was prepared by
and compared with the control. Data were analyzed with Finney’s
probit analysis to determine the LD50 [32]. Etoposide was used as
the standard drug.
mixing Sabouraud (32.5 g), glucose agar (4%) and agareagar (20 g)
ꢁ
in 500 mL of distilled water followed by dissolution at 90e95 C on
a water bath. The media (4 mL) was dispensed into screw-capped
ꢁ
tubes and autoclaved at 121 C for 15 min. Known amounts of
3. Results and discussion
test compounds were added from the stock solution to non-
ꢁ
solidified Sabouraud agar media (50 C). The contents of the
3.1. Spectroscopic studies
tubes were then solidified at room temperature and inoculated
with 4 mm diameter portion of inoculums derived from a 7 days old
respective fungal culture. For non-mycelial growth, an agar surface
The absorption bands observed due to the stretching vibrations
of eOH, eNH and C]O groups in the IR spectrum of ligand
ꢀ
0
ꢀ
ꢀ
Fig. 2. Supramolecular layer of compound 1 mediated by Sn/N2(3.573 A), Br/H12 (2.900 A) and H3/H3(2.384 A) intermolecular non-covalent interactions.

S. Shujah et al. / Journal of Organometallic Chemistry 759 (2014) 19e26
23
Table 2
ꢀ
ꢁ
Selected bond lengths (A) and bond angles ( ) of complex 1.
Bond lengths
SneO(1)
SneO(2)
SneN(1)
SneC(11)
2.119(2)
2.159(2)
2.194(2)
2.127(3)
SneC(13)
N(1)eN(2)
N(1)eC(7)
N(2)eC(8)
2.129(3)
1.403(4)
1.293(3)
1.314(3)
Bond angles
O(1)eSneO(2)
O(1)eSneN(1)
O(1)eSneC(11)
O(1)eSneC(13)
O(2)eSneN(1)
O(2)eSneC(11)
O(2)eSneC(13)
N(1)eSneC(11)
154.91(7)
82.55(8)
92.07(11)
94.14(11)
72.43(8)
94.53(10)
97.11(11)
109.40(11)
N(1)eSneC(13)
C(11)eSneC(13)
SneO(1)eC(1)
SneO(2)eC(8)
SneN(1)eN(2)
SneN(1)eC(7)
SneC(11)eC(12)
SneC(13)eC(14)
112.86(9)
137.73(10)
133.15(18)
114.83(19)
116.43(16)
128.7(2)
Fig. 3. Molecular structure of compound 2, hydrogen atoms are omitted for clarity.
109.7(2)
112.29(19)
disappear in all the complexes. This suggests coordination of
phenolic and enolic oxygens to the diorganotin(IV) moieties after
enolization and subsequent deprotonation processes. The
band is shifted to lower frequency indicating the coordination of
azomethine nitrogen to tin center [33]. The band due to (NeN) is
y(C]N)
complexes show a downfield shift of all carbon resonances,
compared with that of the ligand. This may be a consequence of an
electron density shift from the ligand to the diorganotin(IV) moi-
y
ꢀ1
shifted to higher frequencies at 1072e1082 cm in the spectra of
organotin(IV) complexes (1e4). An increase in the frequency of this
band is attributed to an increase in bond length and decrease in
repulsion of the lone pairs of electrons on the nitrogen atoms
1
119
13
eties. In organotin(IV) compounds, the J [ Sn, C] value is an
important parameter and is used to establish the coordination
around tin in solution. The calculated coupling constants for com-
pounds 1e4 were found to be in the range 599e627 Hz, which
further support the idea of penta-coordination around the Sn atom
in solution for complexes 1e4 [37].
ꢀ
19,34]. The presence of IR bands in the regions of 560e590 cm
1
[
ꢀ
1
and 451e466 cm
indicate the formation of SneO and SneN
bonds, respectively [35].
119
The 1H NMR signals in the ligand due to eOH, CHO and e
The
Sn NMR spectra of diethyl, di-n-butyl, di-n-octyl and
butylchlorotin(IV) complexes show only one sharp resonance
NHN ¼ protons disappeared in the diorganotin(IV) complexes (1e
1
19
at ꢀ192.5, ꢀ190.3, ꢀ198 and ꢀ200 ppm, respectively. The
Sn
4
), due to the conversion of amido form of the ligand to iminol form
chemical shift values are typical of five-coordinated diorganotin(IV)
compounds and indicate similar environment around the two tin
atoms in each complex [38e41].
(
Scheme 1a) and subsequent deprotonation. The downfield shift in
3
119
1
the eCH]N proton resonance to 8.46e8.51 ppm with J ( Sn, H)
coupling constant of 41 Hz confirmed the shift of electron density
from azomethine nitrogen to Sn atom. This coordination was
further confirmed by the single crystal X-ray structures of com-
pounds 1 and 2. All the other protons of the ligand and the Sn
bonded R groups have also been assigned, which are in good
agreement with reported values [36].
3.2. X-ray crystal structure of complexes (1 and 2)
The asymmetric unit of centrosymmetric binuclear complexes 1
and 2 consists of half of the molecule. The molecular structure and
atomic numbering scheme for the two molecules is given in Figs. 1
and 3. The crystallographic data, selected bond lengths and angles
of the homobimetallic molecule of complex 1 and 2 are listed in
Tables 1e3. The structure of binuclear complexes 1 and 2 consists of
a deprotonated ONO tetrabasic hexadentate ligand bonded to two
The characteristic resonance peaks in 3C NMR spectra of the
1
13
3
complexes were recorded in CDCl . The C NMR spectra of the
Table 1
Crystal data and structure refinement parameters for complexes 1 and 2.
R
O
2
Sn(IV) moieties via two oxygen and a nitrogen atom, forming a
NC core around each Sn atom. The SneO(1) and SneO(2) bond
Complex no.
1
2
2
2
Empirical formula
Formula mass
Crystal system
Space group
(C14
889.84
2
H18BrN O
2
Sn)
2
(C18
1002.06
2
H26BrN O
2
Sn)
2
ꢀ
ꢀ
lengths {2.119(2) and 2.159(2) A for 1 and {2.120(2) and 2.143(2) A
for 2} are less than the sum of van der Waals radii of Sn and O
Monoclinic
C2/c, 15
19.115(2)
10.389(13)
17.299(2)
90.00
113.35(15)
90.00
3154.2(6)
4
Orthorhombic
Pbca
9.705(17)
16.165(3)
24.704(4)
90.00
90.00
90.00
3875.4(12)
4
Block
ꢀ
(
3.68 A). The O(1)eSneN(1), O(1)eSn(1)eO(2) and O(2)eSneN(1)
ꢀ
ꢁ ꢁ ꢁ ꢁ
angles are 82.55(8) , 154.91(7) and 72.43(8) for 1 and 81.92(9) ,
a (A)
ꢀ
ꢁ
ꢁ
b (A)
154.53(8) and 72.91(9) for 2, respectively. The SneN(1) bond
ꢀ
c (A)
ꢀ
distance is 2.194(2) and 2.189(2) A for 1 and 2, respectively, com-
parable with the sum of the covalent radii of Sn and N (2.15 A) and
ꢁ
a
b
g
( )
ꢀ
ꢁ
( )
ꢁ
( )
ꢀ
3
V (A )
Table 3
Z
ꢀ
ꢁ
Selected bond lengths (A) and bond angles ( ) of complex 2.
Crystal habit
Size (mm)
Block
0.41 ꢂ 0.33 ꢂ 0.28 0.47 ꢂ 0.23 ꢂ 0.14
Bond lengths
T (K)
r
100 (1)
1.874
41.56
1736
100 (1)
1.717
33.93
1992
SneO(1)
SneO(2)
SneN(1)
SneC(11)
2.120(2)
2.143(2)
2.189(2)
2.121(3)
SneC(15)
N(1)eN(2)
N(1)eC(7)
N(2)eC(8)
2.108(3)
1.403(4)
1.293(4)
1.316(4)
(g cm 3
ꢀ
)
m
(Mo K
a
) (cmꢀ1)
F(000)
Total reflections
Independent reflections
14,013
3866
3259
23,508
3913
3189
Bond angles
O(1)eSneO(2)
O(1)eSneN(1)
O(1)eSneC(11)
O(1)eSneC(15)
O(2)eSneN(1)
O(2)eSneC(11)
O(2)eSneC(15)
N(1)eSneC(11)
154.53(8)
81.92(9)
95.19(11)
90.56(11)
72.91(9)
96.54(11)
95.88(11)
108.87(11)
N(1)eSneC(15)
C(11)eSneC(15)
SneO(1)eC(1) 1
SneO(2)eC(8)
SneN(1)eN(2)
SneN(1)eC(7)
SneC(11)eC(12)
SneC(15)eC(16)
113.64(11)
137.49(12)
32.0(2)
114.59(19)
116.19(18)
128.6(2)
For (F
R(F) ¼ S(jjF
for F
o
ꢃ
s
(F
j ꢀ jF
(F
o
))
o
c
jj)/SjF
o
j,
0.0290
0.0334
o
>
s
o
)
2
2
2
)2]/S[w(F
2 2 1/2
wR(F ) ¼ [S[w(F
o
ꢀ F
c
o
) ]]
0.0712
1.051
2.56e29.43
3866/0/183
0.0827
1.091
2.58e29.42
3913/0/219
Goodness-of-fit
q
Range (deg)
111.9(2)
112.2(2)
Data/restrictions/params

24
S. Shujah et al. / Journal of Organometallic Chemistry 759 (2014) 19e26
ꢀ
ꢀ
Fig. 4. Supramolecular wavy layers of compound 2 mediated by Sn/N2(3.632 A) and Br/
p
(3.539 A) intermolecular interactions.
ꢀ
less than the sum of the van der Waals radii (3.75 A) confirming a
strong tinenitrogen bond. The Sn atom and the O(1), C(1), C(6),
C(7), N(1) atoms form a six membered ring, while the Sn atom and
O(2), C(8), N(2) and N(1) atoms form a five membered ring. The
flexibility present in the butylene linker allows the complexes to
adopt different orientations when relating the two diorganotin(IV)
moieties. The extended structures of 1 and 2 reveal that the
butylene chains of these structures adopt an antiperiplanar or
synthesized bis[diorganotin(IV)] complexes (1e4) were screened
for their antibacterial activity against 2 g positive (B. subtilis, S.
aureus) and 4 g negative bacteria (E. coli, S. flexenari, P. aeruginosa
and S. typhi). The bacterial activity of ligand is reported in a pre-
vious study [29]. The results of present investigation are presented
in Fig. 5. The bis[diorganotin(IV)] complexes (1e4) exhibited
elevated inhibitory activity against gram positive bacteria as their
polyglycane outer layer is loosely packed to facilitate deep pene-
tration of the complex inside the cell to interact with the cyto-
plasmic membrane. On the other hand, a Gram-negative bacterial
cell with a bilayer phospholipid structure protects the inner cyto-
plasmic membrane to a greater degree against the inhibitory action
of the organotin(IV) complex. However, none of the synthesized
complex is more active than the reference drug. Bis[dibutyltin(IV)]
complex (2) was found to be the most potent bactericide and
showed the highest antibacterial activity against B. subtilis, S. aureus
and S. typhi. Bis[chlorodibutyltin(IV)] complex (4) exhibited mild
toxicity to all bacterial strains. S. typhi was resistant against all
compounds except bis[dibutyltin(IV)] complex (2). Survey of liter-
ature shows that other organotin(IV) resistant bacteria have also
been isolated and characterized. However, details of bacterial
2
zigzag conformation [42]. The R Sn(IV) groups are disposed at trans
conformation in the crystalline structure due to packing effects and
it can be supposed that in solution there is a fast dynamic equi-
librium between the different possible conformations [43].
The
five-coordinated metal and can be calculated by using equation
¼ ( )/60 [39], where and are the consecutive largest of the
basal angles around the Sn atom. For five-coordinated Sn with
perfect trigonal-bipyramidal geometry value is one whereas a
value of zero corresponds to a perfect square-pyramidal structure.
The value 0.5 for a molecule indicates a geometry midway be-
tween trigonal bipyramidal and square-pyramidal. The calculated
s value is an important parameter to decide the geometry of
s
b
ꢀ
a
b
a
s
s
s
values 0.29 and 0.28 (1 and 2) indicates a highly distorted square
pyramidal arrangement around each tin atom.
Packing diagram offers a supramolecular structure to compound
ꢀ
0
ꢀ
(
1) mediated by Sn/N2 (3.573 A), Br/H12 (2.900 A) and
ꢀ
H3/H3(2.384 A) intermolecular non-covalent interactions (Fig. 2).
Similarly complex (2) also exhibit a supramolecular wavy layer
ꢀ
ꢀ
structure mediated by Sn/N2(3.632 A) and Br/
p
(3.539 A) inter-
molecular interactions (Fig. 4).
4
. Biological activities
4.1. Antibacterial activity
The need for more potent and specific antimicrobial agents
continues to grow, since the pathogenic microbes develop resis-
tance against such compounds due to gene mutation. Thus, the
4
Fig. 5. Antibacterial activity of H L and its organotin(IV) derivatives against various
bacteria.

S. Shujah et al. / Journal of Organometallic Chemistry 759 (2014) 19e26
25
resistance mechanisms are still poorly understood [44,45]. Bis
dioctyltin(IV)] complex (3) showed insignificant antibacterial ac-
tivity against all tested bacteria.
The bacterial growth inhibition may be due to bactericide effects
or bacteriostatic effects of compounds. The inhibitory action of
organotin(IV) derivatives can be understood by considering chela-
tion theory and is believed to be due to their ability to inhibit
cellular respiration and ATP synthesis. The parent ligand on che-
lation reduces the polarity of the central tin atom primarily because
of the partial sharing of its positive charge with the donor groups
Table 4
Brine Shrimp (Artemia salina) lethality bioassay of N1 ,N6 -bis(5-bromo-2-
0
0
[
hydroxybenzylidene)adipodihydrazide and its bis[diorganotin(IV)] complexes.
Sample code
LD50 g/mL)
H
4
L
1
2
3
4
(
m
e
e
24.65
e
e
Standard drug etoposide, LD50 7.46
m
g/mL.
compounds. The results are presented in Table 4. The toxicity of the
organotin(IV) compounds vary significantly according to their
substitution and within the same substituent series depends on the
lipophilic character of alkyl group [50]. Compound (2) show highest
and possible
p-electron delocalization within the whole chelate
ring. The lipophilic nature of the central Sn atom increases, which
favors the permeation of the complexes through the lipid layer of
the cell membrane. The alkyl groups bonded to the tin atom also
play a significant role in the diffusion of metal complex through the
bacterial cell wall [46,47].
toxicity with LD50 24.65
. Conclusions
Four new homobimetallic diorganotin(IV) derivatives com-
mg/mL.
5
4.2. Antifungal activity
1
0
6
0
pounds of N ,N -bis(5-bromo-2-hydroxybenzylidene)adipodihy-
drazide have been synthesized and characterized by FT-IR, NMR,
mass spectroscopy and elemental analysis. The single crystal
analysis of the bis[diethyl] (2) and bis[dibutyltin(IV)] (3) derivatives
showed homobimetallic nature of these compounds in which each
Sn atom is in distorted square pyramidal geometry. The tendency
towards the said geometry may be due to intermolecular Sn/N
4
The in vitro antifungal activities of ligand H L and bis[dio-
rganotin(IV)] complexes (1e4) were evaluated against six human
pathogenic fungal strains including yeasts (C. albicans ATCC 2192, C.
glabrata ATCC 90030), dermatophytes (M. canis ATCC 9865, T.
longifusus ATCC 22397), opportunistic molds (A. flavus ATCC 1030
and F. solani ATCC 11712) using the agar tube dilution Test.
Amphotericin-B and Miconazole were used as standard drug. The
results are depicted in Fig. 6. The ligand was found active only
against A. flavus. All the complexes were active against F. solani and
the highest antifungal activity was shown by bis[dibutyltin(IV)]
complex (2). However, all the compounds have lower activity than
the standard drug. The bis[diorganotin(IV)] complexes (1,3,4)
showed 20e30% inhibition against A. flavus. T. longifusus, C. albicans,
and M. canis. The complete mechanism of antifungal activity is not
fully understood, however, the activity of ligand and complexes can
be rationalized in terms of hydrogen bond formation between the
azomethinic nitrogen of the synthesized compound and some bio-
receptors in the cells of microorganisms causing disruption in the
movement of ribosome along with RNA consequently the synthesis
of protein and DNA in the cell nucleus is blocked [48,49].
interaction. Moreover, Sn/N and Br/p interactions were found to
assemble molecules to form fancy supramolecular architecture in
both compounds. These compounds were found active against
studied bacteria, and fungi. The highest cytotoxicity was noted for
complex 2 (LD50 24.65 mg/mL).
Acknowledgments
The authors are thankful to Higher Education Commission of
Pakistan for financial support.
Appendix A. Supplementary material
2 2 2 2
CCDC 962695 for (Et Sn) L (1) and 962694 for (Bu Sn) L (2)
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
4
.3. Cytotoxicity
Organotin(IV) complexes exert their toxic effects on cells by
preventing the mitochondrial oxidative phosphorylation, inducing
DNA damage, apoptosis or necrosis. The in vivo lethality to brine
shrimp nauplii was used to assess the cytotoxicity of synthesized
References
[
[
[
[
[
1] M. Nath, S. Pokharia, R. Yadav, Coord. Chem. Rev. 215 (2001) 99e149.
2] M. Gielen, Met.-Based Drugs 1 (1994) 213e219.
3] L. Pellerito, L. Nagy, Coord. Chem. Rev. 224 (2002) 111e150.
4] P. Yang, M. Guo, Coord. Chem. Rev. 185 (1999) 189e211.
5] A.J. Crowe, P.J. Smith, C.J. Cardin, H.E. Parge, F.E. Smith, Cancer Lett. 24 (1984)
45e48.
[6] V.I. Bregadze, S.A. Glazun, P.V. Petrovskii, Z.A. Starikova, V.Y. Rochev, H. Dalil,
M. Biesemans, R. Willem, M. Gielen, D. de Vos, Appl. Organomet. Chem. 17
(2003) 453e457.
[7] L.S. Zamudio-Rivera, R. George-Tellez, G. López-Mendoza, A. Morales-Pacheco,
E. Flores, H. Höpfl, V. Barba, F.J. Fernández, N. Cabirol, H.I. Beltrán, Inorg. Chem.
44 (2005) 5370e5378.
[
[
8] H.D. Yin, Q.B. Wang, S.C. Xue, J. Organomet. Chem. 689 (2004) 2480e2485.
9] S. Shuja, S. Ali, M.N. Tahir, N. Khalid, I.U. Khan, Acta Cryst. E 64 (2008) m531e
m532.
[
[
10] C. Ma, Y. Han, R. Zhang, J. Inorg. Organomet. Polym. Mater. 17 (2007) 541e546.
11] S. Shuja, Zia-ur-Rehman, N. Muhammad, S. Ali, N. Khalid, M.N. Tahir,
J. Organomet. Chem. 696 (2011) 2772e2781.
[12] N. Terzioglu, A. Gürsoy, Eur. J. Med. Chem. 38 (2003) 781e786.
[13] M.T. Cocco, C. Congiu, V. Lilliu, V. Onnis, Bioorg. Med. Chem. 14 (2006) 366e372.
[14] J. Easmon, G. Puerstinger, T. Roth, H.H. Fiebig, M. Jenny, W. Jaeger, G. Heinisch,
J. Hofmann, Int. J. Cancer 94 (2001) 89e96.
[
15] P. Vicini, F. Zani, P. Cozzini, I. Doytchinova, Eur. J. Med. Chem. 37 (2002) 553e564.
Fig. 6. Antifungal activity of H
4
L and its organotin(IV) derivatives against various
[16] J. Patole, U. Sandbhor, S. Padhye, D.N. Deobagkar, C.E. Anson, A. Powell, Bioorg.
bacteria.
Med. Chem. Lett. 13 (2003) 51e55.

26
S. Shujah et al. / Journal of Organometallic Chemistry 759 (2014) 19e26
[
17] A. Walcourt, M. Loyevsky, D.B. Lovejoy, V.R. Gordeuk, D.R. Richardson, Int. J.
[33] C. Pettinari, F. Marchetti, R. Pettinari, D. Martini, A. Drozdov, S. Troyanov,
Inorg. Chim. Acta 325 (2001) 103e114.
Biochem. Cell Biol. 36 (2004) 401e407.
[
[
[
18] A.M. Stadler, J. Harrowfield, Inorg. Chim. Acta 362 (2009) 4298e4314.
19] H.D. Yin, J.C. Cui, Y.L. Qiao, Polyhedron 27 (2008) 2157e2166.
20] D.K. Dey, S.P. Dey, N.K. Karan, A. Ly ꢁc ka, G.M. Rosair, J. Organomet. Chem. 749
[34] M.A. Ali, A.H. Mirza, A.L. Tan, L.K. Wei, P.V. Bernhardt, Polyhedron 23 (2004)
2037e2043.
[35] H.D. Yin, M. Hong, G. Li, D.Q. Wang, J. Organomet. Chem. 690 (2005) 3714e
3719.
(
2014) 320e326.
[
[
[
[
21] S. Shujha, A. Shah, Zia-ur-Rehman, N. Muhammada, S. Ali, R. Qureshi,
N. Khalid, A. Meetsma, Eur. J. Med. Chem. 45 (2010) 2902e2911.
22] S. Shujah, Zia-ur-Rehman, N. Muhammad, A. Shah, S. Ali, N. Khalid,
A. Meetsma, J. Organomet. Chem. 741 (2013) 59e66.
23] D.D. Perrin, W.L.F. Armengo, Purification of Laboratory Chemicals, third ed.,
Pergamon Press, Oxford, 1988.
24] Bruker, Smart, SAINTPLUS and XPREP, Area Detector Control and Integration
Software. Smart Apex Software Reference Manuals, Bruker Analytical X-ray
Instruments, Inc., Madison, Wisconsin, USA, 2006.
[36] Zia-ur-Rehman, N. Muhammad, S. Shuja, S. Ali, I.S. Butler, A. Meetsma,
M. Khan, Polyhedron 28 (2009) 3439e3448.
[37] M. Nádvorník, J. Holeek, K. Handlí, A. Lyka, J. Organomet. Chem. 275 (1984)
43e51.
[38] J.M. Rivera, H. Reyes, A. Cortés, R. Santillan, P.G. Lacroix, C. Lepetit, K. Nakatani,
N. Farfán, Chem. Mater. 18 (2006) 1174e1183.
[39] N. Farfán, T. Mancilla, R. Santillan, A. Gutiérrez, L.S. Zamudio-Rivera,
H.I. Beltrán, J. Organomet. Chem. 689 (2004) 3481e3491.
[40] H. Reyes, C. García, N. Farfán, R. Santillan, P.G. Lacroix, C. Lepetit, K. Nakatani,
J. Organomet. Chem. 689 (2004) 2303e2310.
[41] B. Wrackmeyer, Annu. Rep. NMR Spectrosc. 16 (1985) 73.
[42] N.K. Ngan, M.K. Lo, C.S.R. Wong, Polyhedron 33 (2012) 235e251.
[43] V. Barba, E. Vega, R. Luna, H. Höpfl, H.I. Beltrán, L.S. Zamudio-Rivera,
J. Organomet. Chem. 692 (2007) 731e739.
[44] A. Cruz, T. Caetano, S. Suzuki, S. Mendo, Mar. Environ. Res. 64 (2007) 639e650.
[45] U. Roy, D. Nair, Ecotoxicology 16 (2007) 253e261.
[46] N. Muhammad, Zia-ur-Rehaman, S. Shujah, A. Shah, S. Ali, A. Meetsma,
Z. Hussain, J. Coord. Chem. 65 (2012) 3766e3775.
[
25] P.T. Beurskens, G. Beurskens, R. Gelder, S. García-Granda, S.R.O. Gould,
R. Israël, J.M.M. Smits, The DIRDIF-99 Program System, Crystallography Lab-
oratory, University of Nijmegen, The Netherlands, 1999.
[
[
[
[
26] G.M. Sheldrick, SHELXL-97, Program for the Refinement of Crystal Structures,
University of Göttingen, Germany, 1997.
27] A. Meetsma, PLUTO, Molecular Graphics Program, University of Groningen,
The Netherlands, 2007.
28] A.L. Spek, PLATON, Program for the Automated Analysis of Molecular Geom-
etry, University of Utrecht, The Netherlands, 2006.
29] T. Sedaghat, M. Aminian, G. Bruno, H.A. Rudbari, J. Organomet. Chem. 737
[47] K. Fukushima, S.K. Dubey, S. Suzuki, J. Gen. Appl. Microbiol. 58 (2012)
283e289.
(
2013) 26e31.
[
[
30] W. Rehman, M.K. Baloch, A. Badshah, Eur. J. Med. Chem. 43 (2008) 2380e2385.
31] A. Rahman, M.I. Choudhary, W.J. Thomsen, Bioassay Techniques for Drug
Development, Harward Academic Press, Amsterdam, 2001, p. 14.
[48] P. Chaudhary, M. Swami, D.K. Sharma, R.V. Singh, Appl. Organomet. Chem. 23
(2009) 140e149.
[49] G.A. Ayoko, J.J. Bonire, S.S. Abdulkadir, P.F. Olurinola, J.O. Ehinmidu, S. Kokot,
S. Yiasel, Appl. Organomet. Chem. 17 (2003) 749e758.
[50] M. Nath, Appl. Organomet. Chem. 22 (2008) 598e612.
[32] D.J. Finney, Probit Analysis, third ed., Cambridge University Press, Cambridge,
1971.