Organotin(IV) 4-methoxyphenylethanoates: Synthesis, spectroscopic characterization, X-ray structures and in vitro anticancer activity against human prostate cell lines (PC-3)

Article abstract of DOI:10.1016/j.ica.2009.01.003

A series of organotin(IV) carboxylates, [Bu₂SnL₂] (1), [Et₂SnL₂] (2), [Me₂SnL₂] (3), [Bu₃SnL]_n (4), [Me₆Sn₂L₂]_n (5), [Ph

Full text of DOI:10.1016/j.ica.2009.01.003

Inorganica Chimica Acta 362 (2009) 2842–2848
Contents lists available at ScienceDirect
Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Organotin(IV) 4-methoxyphenylethanoates: Synthesis, spectroscopic
characterization, X-ray structures and in vitro anticancer activity against
human prostate cell lines (PC-3)
b
a
Niaz Muhammad a, Zia-ur-Rehman a, Saqib Ali a, , Auke Meetsma , Farkhanda Shaheen
*
a Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan
b Crystal Structure Center, Chemical Physics, Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, NL-9747 AG Groningen, The Netherlands
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 August 2008
Received in revised form 7 November 2008
Accepted 3 January 2009
Available online 10 January 2009
A
series of organotin(IV) carboxylates, [Bu2SnL2] (1), [Et2SnL2] (2), [Me2SnL2] (3), [Bu3SnL]n (4),
[Me6Sn2L2]n (5), [Ph3SnL]n (6) and [Oct2SnL2] (7), where L = O2CCH2C6H4OCH3-4, have been synthesized.
These complexes have been characterized by elemental analysis, FT-IR and multinuclear NMR (1H, 13C
and 119Sn). Based on spectroscopic results, the ligand appeared to coordinate to the Sn atom through
COO moiety. Single crystal analysis has shown a bridging behavior of ligand in tributyl- and trimethyl-
tin(IV) derivatives, and a chelating bidentate mode in diethyltin(IV) complex. Bioassay results have
shown that these compounds have good antibacterial, antifungal and antitumor activity. The activity
against prostate cancer cell lines (PC-3) decreased in the order 1 > 5 > 2 > 3 > 7.
Keywords:
Organotin(IV)
4-Methoxyphenylethanoate
Crystal structures
Antibacterial
Ó 2009 Elsevier B.V. All rights reserved.
Antifungal
Prostate cell lines (PC-3)
1. Introduction
bridging bidentate ligand [15]. Generally, triorganotin(IV) carbox-
ylates with bulky R groups attached to the Sn atom will favor tet-
The chemical properties, biological significance, industrial
importance and structural characterization of organotin(IV) com-
plexes are well documented. They have a broad spectrum of appli-
cations, being used in antifouling paints [1–3], PVC stabilization
[4], as homogeneous catalysts [5], and as ion carriers in electro-
chemical membranes design [6]. Among organotin(IV) complexes,
organotin (IV) carboxylates show significant antifungal, antibacte-
rial and antitumor activities [7–11] which is essentially related to
the number and nature of the organic groups attached to the cen-
tral Sn atom, however, the role of carboxylate ligand cannot be ig-
nored [9]. Usually triorganotin(IV) compounds display a higher
biological activity than their di- and monoorganotin(IV) analogues,
which has been related to their ability to bind to proteins [12–14].
In addition to their biological activities, the organotin(IV) carboxyl-
ates also present an interesting structural diversity. Depending on
the mode of attachment of the carboxylate group, the resultant tri-
organotin(IV) complex can either be four- or five-coordinated. A
tetrahedral complex results when the carboxylate group acts as a
monodentate ligand [15]. For a bridged carboxylate group, a penta-
coordinated polymer usually results while a chelated monomeric
compound is formed when the carboxylate ligand acts as a non-
rahedral monomeric structures, while sterically less demanding R
groups would favor bridged polymeric structures [16]. Among
diorganotin(IV) bis(carboxylates) the coordination geometry
around the Sn atom is usually found to be skew trapezoidal [17].
In such type of structural motif the Sn atom is hexa-coordinated
and carboxylate ligands chelate the Sn atom, forming disparate
Sn–O bond distances. In continuation of our previous work [18],
we report here synthesis, spectroscopic characterization of organo-
tin(IV) 4-methoxyphenylethanoates and their antibacterial, anti-
fungal, cytotoxicity and antitumor activity against human
prostate cell lines (PC-3).
2. Experimental
All the diorganotin(IV) and triorganotin(IV) precursors were
purchased from Aldrich and were used without further purifica-
tion. All the solvents were dried according to reported procedures
[19]. The melting points were recorded on an electrothermal melt-
ing point apparatus, model MP-D mitamura Riken Kogyo (Japan).
Microanalysis was done using a Leco CHNS 932 apparatus. IR spec-
tra were recorded using KBr pellets in the range from 4000 to
400 cmꢀ1 using a bio-Rad Excaliber FT-IR, model FTS 300 MX spec-
trometer (USA). 1H and 13C NMR spectra were recorded at room
temperature in CDCl3 on a Bruker Advance Digital 300 MHz NMR
* Corresponding author.
E-mail address: drsa54@yahoo.com (S. Ali).
0020-1693/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2009.01.003

N. Muhammad et al. / Inorganica Chimica Acta 362 (2009) 2842–2848
2843
spectrometer (Switzerland) and a Varian Unity 500-MHz instru-
ment [119Sn; SnMe4(ext) ref].
117Sn–13C) = 355/339 Hz], 27.8 [C-b, 2J(119Sn–13C) = 20 Hz], 27.0
[C-
3J(119Sn–13C) = 63 Hz], 13.7 (C-d). 119Sn NMR (CDCl3, ppm):
c,
107.0.
2.1. Synthesis
2.1.6. Trimethyltin(IV) 4-methoxyphenylethanoate (5)
2.1.1. Synthesis of sodium 4-methoxyphenylethanoate
Compound 5 was prepared in the same way as 1, using equimo-
lar molar amounts. The product was recrystallized from chloro-
form and n-hexane (4:1) mixture (Yield: 1.27 g, 77%). M.p.
148–149 °C. Anal. Calc. for C12H18O3Sn: C, 43.64; H, 5.45. Found:
The sodium salt of ligand, R0COONa, was prepared by dropwise
addition of an equimolar amount of sodium hydrogen carbonate
dissolved in distilled water to a methanolic solution of ligand acid
(R0COOH). The solution was stirred for 2 h at room temperature
and was evaporated under reduced pressure to give a white solid
which was vacuum dried.
C, 43.61; H, 5.48%. IR (cmꢀ1): 1561
m(OCO)asym, 1394 m(OCO)sym,
546
m
(Sn–C), 472
m
(Sn–O). 1H NMR (CDCl3, ppm): 3.58 (s, H2,
0
0
2H), 7.22 (d, H4,4 , 2H), 6.87 (d, H5,5 , 2H), 3.81 (s, H7, 3H), 0.55 [s,
H , 9H, 2J(119/117Sn–1H) = 58/56 Hz]. 13C NMR (CDCl3, ppm): 177.4
a
2.1.2. Dibutyltin(IV) bis(4-methoxyphenylethanoate) (1)
(C-1), 40.9 (C-2), 127.7 (C-3), 130.2 (C-4,40), 113.8 (C-5,50), 158.3
The sodium salt R0COONa (0.94 g, 5 mmol), was refluxed for
10 h with dibutyltin(IV) dichloride (0.76 g, 2.5 mmol) in dry tolu-
ene contained in a 250 ml two necked round bottom flask. A turbid
solution obtained, was left overnight at room temperature. The so-
dium chloride formed was filtered off and the filtrate was rotary
evaporated. The resultant solid mass was recrystallized from chlo-
roform and n-hexane (4:1) mixture (Yield: 1.11 g, 79%). M.p. 69–
72 °C. Anal. Calc. for C26H36O6Sn: C, 55.32; H, 6.38. Found: C,
(C-6), 55.2 (C-7), 2.4 [C-
NMR (CDCl3, ppm): ꢀ139.2.
a,
1J(119/117Sn–13C) = 395/377 Hz]. 119Sn
2.1.7. Triphenyltin(IV) 4-methoxyphenylethanoate (6)
Compound 6 was prepared in the same way as 1, using equimo-
lar molar amounts. The product was recrystallized from chloro-
form and n-hexane (4:1) mixture (Yield: 1.91 g, 74%). M.p. 294–
298 °C. Anal. Calc. for C27H24O3Sn: C, 62.79; H, 4.65. Found: C,
55.29; H, 6.41%. IR (cmꢀ1): 1542
m
(OCO)asym, 1427
m
(OCO)sym
,
62.75; H, 4.68%. IR (cmꢀ1): 1576
m
(OCO)asym, 1392
m
(OCO)sym, 459
(Sn–O).1H NMR (CDCl3, ppm): 3.62 (s, H2, 4 H),
m
(Sn–O). 1H NMR (CDCl3, ppm): 3.71 (s, H2, 2H), 7.22 (d, H4,4 ,
0
532
m
(Sn–C), 465
m
0
0
0
0
7.23 (d, H4,4 , 4H), 6.87(d, H5,5 , 4H), 3.80 (s, H7, 6H), 1.50–1.64
2H), 6.86 (d, H5,5 , 2H), 3.81(s, H7, 3H), 7.74–7.71 (m, Hb,b , 6H),
(m, H ,b, 8H), 1.24–1.34 (m, H , 4H), 0.83 (t, Hd, 6H). 13C NMR
7.47–7.45 (m, H ,d, 9H). 13C NMR (CDCl3, ppm): 178.9 (C-1),
a
c
c,
c0
(CDCl3, ppm): 182.2 (C-1), 40.2 (C-2), 126.5 (C-3), 130.2 (C-4,40),
40.3 (C-2), 128.9 (C-3), 130.3 (C-4,40), 113.9 (C-5,50), 158.5 (C-6),
114.0
1J(119Sn–13C) = 790 Hz], 26.5 [C-b, 2J(119Sn–13C) = 38 Hz], 26.2 [C-
3J(119Sn–13C) = 98 Hz], 13.5 (C-d). 119Sn NMR (CDCl3, ppm):
(C-5,50),
158.6
(C-6),
55.3
(C-7),
25
[C-a,
55.3 (C-7), 138.1 [C-a,
1J(119Sn–13C) = 640 Hz], 136.9 [C-b,
2J(119Sn–13C) = 48 Hz], 128.9 [C- 3J(119Sn–13C) = 63 Hz], 130.2
c,
c,
[C-d, 4J(119Sn–13C) = 13.5 Hz]. 119Sn NMR (CDCl3, ppm): ꢀ113.2.
ꢀ240.1.
2.1.8. Dioctyltin(IV) bis(4-methoxyphenylethanoate) (7)
2.1.3. Diethyltin(IV) bis(4-methoxyphenylethanoate) (2)
The ligand acid, R0COOH (0.83 g, 5 mmol) and dioctyltin(IV)
oxide (0.90 g, 2.5 mmol), were suspended in dry toluene (100 ml)
in a single necked round bottom flask (250 ml), equipped with a
Dean-Stark apparatus. The mixture was refluxed for 10 h and water
formed during the condensation reaction was removed at regular
intervals. A clear solution thus obtained, was cooled to room tem-
perature and solvent was removed under reduced pressure. The so-
lid obtained was recrystallized from chloroform and n-hexane
(4:1) mixture. (Yield: 1.32 g, 78%). M.p. 90–92 °C. Anal. Calc. for
C34H52O6Sn: C, 60.36; H, 7.69. Found: C, 60.32; H, 7.73%. IR
Compound 2 was prepared and was recrystallized in the same
way as 1. (Yield: 2.18 g, 86%). M.p. 98 °C. Anal. Calc. for C22H28O6Sn:
C, 51.97; H, 5.51. Found: C, 51.95; H, 5.53%. IR (cmꢀ1): 1510
m
(OCO)asym, 1377
m
(OCO)sym, 505
m
(Sn–C), 484
m
(Sn–O). 1H NMR
0
0
(CDCl3, ppm): 3.64 (s, H2, 4H), 7.23 (d, H4,4 , 4H), 6.87 (d, H5,5
,
4 H), 3.81 (s, H7, 6 H), 1.61 (q, H , 4H), 1.22 (t, Hb, 6H). 13C NMR
a
(CDCl3, ppm): 182.3 (C-1), 40.1 (C-2), 126.5 (C-3), 130.2 (C-4,40),
114.0 (C-5,50), 158.6 (C-6), 55.2 (C-7), 17.3 [C- 1J(119/
a,
117Sn–13C) = 582/562 Hz], 8.8 [C-b, 2J(119Sn–13C) = 43.5 Hz]. 119Sn
NMR (CDCl3, ppm): ꢀ156.8.
(cmꢀ1): 1514
m
(OCO)asym, 1380
m
(OCO)sym
,
525
m
(Sn–C), 483
(Sn–O). 1H NMR (CDCl3, ppm): 3.62 (s, H2, 4H), 7.23 (d, H4,4
,
0
m
0
2.1.4. Dimethyltin(IV) bis(4-methoxyphenylethanoate) (3)
4H), 6.86 (d, H5,5 , 4H), 3.80 (s, H7, 6H), 1.58–1.55 (bs, H ,b, 4H),
a
1.28–1.22 (bs, H , 28H), 0.90 (t, Hd , 6H]. 13C NMR (CDCl3,
0
0
Compound 3 was prepared and was recrystallized in the same
way as 1. (Yield: 1.56 g, 65%). M.p. 76 °C. Anal.Calc. for C20H24O6Sn:
C, 50.00; H, 5.00. Found: C, 50.05; H, 4.98%. IR (cmꢀ1): 1510
c-c
ppm): 182.0 (C-1), 40.2 (C-2), 126.5 (C-3), 130.4 (C-4,40), 114.0
(C-5,50), 158.6 (C-6), 55.2 (C-7), 25.2 [C- 1J(119/117Sn–13C) = 575/
3J(119/
a
,
m
(OCO)asym, 1361
m
(OCO)sym, 573
m
(Sn–C), 498
m
(Sn–O).1H NMR
556 Hz], 24.3 [C-b, 2J(119Sn–13C) = 37 Hz], 33.2 [C-
c,
0
0
(CDCl3, ppm): 3.63 (s, H2, 4H), 7.21 (d, H4,4 , 4H), 6.88 (d, H5,5
,
117Sn–13C) = 95/91 Hz], 33.2 (C-d), 29.1 (C-a0), 29.0 (C-b0), 22.7 (C-
c0), 10.5 (C-d0). 119Sn NMR (CDCl3, ppm): ꢀ150.3.
4H), 3.81(s, H7, 6H), 0.95 [s, H , 6H, 2J(119/117Sn–1H) = 82/79 Hz].
a
13C NMR (CDCl3, ppm): 181.9 (C-1), 40.0 (C-2), 126.3 (C-3), 130.2
(C-4,40), 114.0 (C-5,50), 158.7 (C-6), 55.2 (C-7), 4.2 [C-
a
,
2.2. X-ray crystallographic studies
1J(119Sn–13C) = 703 Hz]. 119Sn NMR (CDCl3, ppm): ꢀ237.8.
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 pro-
gram SAINT [20]. The program suite SAINTPLUS was used for space
group determination (XPREP) [20]. The structure was solved by
Patterson method; extension of the model was accomplished by
direct method and applied to difference structure factors using
the program DIRDIF [21]. Crystal data and numerical details on data
collection and refinement are given in Table 1. All refinement cal-
culations and graphics were performed with the program packages
SHELXL [22] a locally modified version of the program PLUTO and PLA-
TON package [23,24]. The isotropic displacement parameters for
2.1.5. Tributyltin(IV) 4-methoxyphenylethanoate (4)
Compound 4 was prepared in the same way as 1, using equimo-
lar molar amounts. The product was recrystallized from chloro-
form and n-hexane (4:1) mixture. (Yield: 1.86 g, 82%). M.p. 63–
64 °C. Anal. Calc. for C21H36O3Sn: C, 55.26; H, 7.89. Found: C,
55.24; H, 7.91%. IR (cmꢀ1): 1577
m(OCO)asym, 1377 m(OCO)sym,
535
m
(Sn–C), 475
m
(Sn–O). 1H NMR (CDCl3, ppm): 3.57 (s, H2,
0
0
2H), 7.22 (d, H4,4 , 2H), 6.85 (d, H5,5 , 2H), 3.80 (s, H7, 3H), 1.69–
1.53 (m, H , 6H), 1.41–1.22 (m, Hb, , 12H), 0.90 (t, Hd, 9H). 13C
a
c
NMR (CDCl3, ppm): 177.4 (C-1), 41.2 (C-2), 128.0 (C-3), 130.8 (C-
4,40), 113.8 (C-5,50), 158.3 (C-6), 55.2 (C-7), 16.4 [C- 1J(119/
a,

2844
N. Muhammad et al. / Inorganica Chimica Acta 362 (2009) 2842–2848
Table 1
3.2. IR spectra
Crystal data and structure refinement parameters for compounds 2, 4 and 5.
The assignment of IR bands of complexes 1–7 has been made by
comparison with the IR spectra of their related precursors. Appear-
ance of new bands at 498–459 cmꢀ1 and 573–505 cmꢀ1 for all
complexes, which are absent from the spectrum of free ligand,
can be assigned to Sn–O and Sn–C stretching mode of vibrations,
Compound
2
4
5
Moiety
Formula
Formula
Weight
Crystal system
Space group
Unit cell dimensions
a (Å)
b (Å)
C22H28O6Sn
C21H36O3Sn
C24H36O6Sn2
507.13
455.23
657.97
monoclinic
C2/c
monoclinic
P21/c
monoclinic
P21/c
respectively. Of particular interest in the IR spectra is the
a difference between asymmetric and symmetric vibrations of COO
moiety. According to the literature [25],
greater than 250 cmꢀ1
Dm value,
D
m
31.852
5.297
13.659
105.83
2217.1
3.90–23.18
13.016(2)
6.9114(3)
16.8865(3)
10.3679(16)
106.213(23)
2185.4(6)
27.6244(13)
14.1378(7)
93.4095(8)
2694.5(2)
shows a monodentate carboxylate moiety, a value between 150
and 250 cmꢀ1 indicates a bridging behavior while a difference less
than 150 cmꢀ1 corresponds to a chelate structure. In our present
investigation complexes 1, 2, 3 and 7 show a chelating behavior
while 4–6 illustrate a bridging mode of coordination in solid state.
These observations are further supported by the crystal structures
of complexes 2, 4 and 5.
c (Å)
b (°)
V (Å3)
h Ranges for
data
2.92–26.37
2.64–28.28
collection (°)
Z
4
4
4
qcalc (g cmꢀ3
F(000)
)
1.389
944
1.622
1312
1032
3.3. 1H NMR spectra
Crystal size
(mm)
0.12 ꢁ 0.06 ꢁ 0.015 0.28 ꢁ 0.23 ꢁ 0.08
0.39 ꢁ 0.28 ꢁ 0.13
T (K)
Index ranges
100(1)
100(1)
100(1)
The assignment of the proton resonances were made by their
peak multiplicity, intensity pattern and comparison of the inte-
gration values of the protons with expected composition. A com-
parison of the 1H NMR spectra of all organotin(IV) complexes
with the ligand have shown disappearance of signal for OH
(11.66 ppm) proton on the formation of Sn–O bond. Protons of
alkyl/aryl groups attached to Sn atom give multifaceted pattern
except for compounds 3 and 5, where sharp singlets for CH3
h: ꢀ31 ? 33; k:
ꢀ5 ? 5; l:
ꢀ14 ? 14
10495
h: ꢀ17 ? 17; k:
ꢀ22 ? 22; l:
ꢀ13 ? 13
h: ꢀ9 ? 8; k:
ꢀ36 ? 36; l:
ꢀ18 ? 18
23247
Total data
Unique data
18008
1414 [0.0194]
5332 [0.0341]
6656 [0.0231]
[Rint
Final R indices
[I > /4 (I)]
Final R indices
[I > /2 (I)]
]
R1 = 0.0369,
wR2 = 0.0876
R1 = 0.0244,
wR2 = 0.0589
r
R1 = 0.0185,
wR2 = 0.0608
r
protons are observed with 2J
(
119Sn/117Sn–1H) values, 82/79
and 58/56, respectively. These 2J (119Sn–1H) values correspond
to C–Sn–C bond angles 133.28° and 111.1°, which confirm six
and four coordinated Sn atom in solution in compound 3 and
5, respectively [26].
hydrogen atoms were refined on F2 with full-matrix least-squares
procedures.
3.4. 13C NMR spectra
3. Results and discussion
The 13C NMR chemical shifts due to different R groups attached
to Sn atom were observed at positions comparable to the other
similar compounds [8]. In 13C NMR data, the carbons attached to
Sn atom in all the synthesized compounds have shown satellites
due to nJ [119Sn/17Sn–13C] coupling. The coupling constants are
important indicators for structural elucidation of organotin(IV)
carboxylates. In present study, triorganotin carboxylates (com-
pounds 4, 5 and 6) exhibit 1J (119Sn–13C) being of the order of
355, 395 and 640 Hz, respectively. These values confirm a mono-
meric tetrahedral geometry in solution for these complexes
[27,28]. In complex 6, the 13C chemical shift of the ipso-carbon at
138 ppm further confirm the tetrahedral geometry around Sn
[29]. In case of 1, 2, 3 and 7 1J [119Sn–13C] values and (C–Sn–C)
bond angles are 790 (146.05°), 582 (127.80°), 703 (138.42°) and
575 Hz (127.21°), respectively [8]. These values suggest a decrease
in coordination number of Sn from six to five for compounds 2 and
7 while compounds 1 and 3 exhibit skew-trapezoidal geometry
around Sn atom in solution.
3.1. Synthesis of complexes 1–7
Reaction of R3SnCl/R2SnCl2 with NaL in 1:1/1:2 molar ratios,
and that of R2SnO with HL in 1:2 molar ratios, respectively led to
the formation of complexes according to Eqs. (1)–(3), Scheme 1.
The resulting complexes were obtained in good yield (65-86%).
All the complexes were white solids, stable in air and were soluble
in CHCl3 and DMSO.
R2SnCl2 þ 2NaL ! R2SnL2 þ 2NaCl
R ¼ n-Butyl ð1Þ; Ethyl ð2Þ; Methyl ð3Þ
ð1Þ
R3SnCl þ NaL ! R3SnL þ NaCl
R ¼ n-Butyl ð4Þ; Methyl ð5Þ; Phenyl ð6Þ
ð2Þ
ð3Þ
R2SnO þ 2HL ! R2SnL2 þ H2O R ¼ n-Octyl ð7Þ
H2
H2
4
5
H2
C
C
3.5. 119Sn NMR spectra
C
′
δ
CH3
γ
α
β
′
2
α
1
7
′
3
δ
6
γ
H2C
C
′
OOC H2C
OCH3
β
C
H2
C
H2
H2
The solution structure of the complexes 1–7 was further con-
firmed by 119Sn NMR. The 119Sn NMR spectra of 4–6 displayed
sharp signals at 107.0, 139.2 and ꢀ113.2 ppm, respectively, which
were consistent with those for similar four-coordinate organo-
tin(IV) carboxylates [30,31]. Complexes 2 and 7 gave 119Sn signal
correspond to five-coordinate Sn atom [8], while six-coordinate
geometry was assigned to complexes 1 and 3 on the basis of
119Sn chemical shift [32].
4'
5'
γ
H2
δ
β
α
β
C
CH3
α
γ
α
β
CH3
α
H2C
CH3
δ
H2C
C
H2
γ ′
′
β
Scheme 1.

N. Muhammad et al. / Inorganica Chimica Acta 362 (2009) 2842–2848
2845
Fig. 2. ORTEP drawing of asymmetric unit of compound 4 with numbering scheme.
value is equal to zero for a perfect square-pyramidal and unity
for perfect trigonal-bipyramidal. The calculated
s value for com-
Fig. 1. ORTEP drawing of compound 2 with numbering scheme.
plex 4 is 0.80 whereas for 5, two values 0.82 (Sn1) and 0.89
(Sn2), were obtained. These values indicate a highly distorted tri-
gonal-bipyramidal arrangement around Sn atom. The distortion in
complex 4 is more than 5 that may be due to bulky butyl groups
attached to Sn atom. The angles of axial bonds [O–Sn–O] are
176.01°, in complex 4 and 169.73°, in complex 5 while the sum
of the equatorial C–Sn–C angles are 358.02° and 359.37°, respec-
tively. Thus, carboxylate ligand chelated to two symmetry related
Sn atoms and gave rise to the unequal Sn–O bond distances. The
inequality in the Sn–O bonds is reflected in the associated C–O
bond distances, the longer C–O bond is involved with shorter
3.6. Crystal structure of complex 2, 4 and 5
The molecular structure of the complex 2 is shown in Fig. 1
whereas the crystal data, selected bond lengths and bond angles
are listed in Tables 1 and 2. The geometry at the central Sn atom
is skew-trapezoidal in which the basal plane is defined by four oxy-
gen atoms derived from the two chelating carboxylate ligands
whereas the remaining two positions are occupied by two ethyl
substituents. The carboxylate ligands chelate the Sn center in an
asymmetric way, and are reflected in two shorter Sn–O bonds
and two longer Sn–O bonds. The ethyl groups do not occupy the
exact axial positions as a result C–Sn–C angle is 136.96 (15)° which
falls in the range (122.6–156.9°) for skew-trapezoidal geometry
[33,34]. The asymmetric mode of coordination of the carboxylate
ligands is further confirmed by unequal C–O bond distances;
1.248(3) Å and 1.285(3) Å. The Shorter C–O bond value is for
weakly coordinated O atoms of the ligands. The Sn–C bond dis-
tances, 2.120(3) are in agreement with previous reports [35].
The molecular structure of complex 4 and 5 are shown in Figs.
2 and 4, respectively. The complexes exhibit a carboxylate-
bridged motif in which the Sn center shows trans-R3SnO2 (where
R = CH3, n-Bu) trigonal-bipyramidal coordination, the equatorial
plane being defined by the three R groups while axial positions
are occupied by two oxygen atoms. According to the literature
[36], the geometry around Sn atom can be characterized by the
value of
around the Sn atom. The angle values
a square-pyramidal geometry, and the value of
s
= (b ꢀ
a
)/60, where b is the largest of the basal angles
= b = 180° correspond to
= 120° corre-
Fig. 3. The ID chain structure of compound 4, propagation via O ? Sn Coordination.
a
a
sponds to a perfect trigonal-bipyramidal geometry. Thus, the
s
Table 2
Selected bond length (Å) and bond angles (°) of compound 2.
Bond length (Å)
Sn1–C30
Sn1–O15
Sn1–C30–2
Sn1–O16
2.120(3)
2.543(2)
2.120(3)
2.1140(18)
Sn1–O15–2
Sn1–O16–2
O15–C8
2.543(2)
2.1140(18)
1.248(3)
1.285(3)
O16–C8
Bond angles (°)
C30–Sn1–C30–2
C30–Sn1–O16
136.96(15)
107.06(9)
105.39(9)
105.39(9)
107.06(9)
80.75(9)
O16–Sn1–O15–2
O16–2–Sn1–O15–2
C30–Sn1–O15
C30–2–Sn1–O15
O16–Sn1–O15
135.57(7)
54.86(7)
87.81(10)
88.37(10)
54.86(7)
C30–2–Sn1–O16
C30–Sn1–O16–2
C30–2–Sn1–O16–2
O16–Sn1–O16–2
C30–Sn1–O15–2
C30–2–Sn1–O15–2
O16–2–Sn1–O15
O15–2–Sn1–O15
135.57(7)
169.57(10)
88.37(10)
87.81(10)
Fig. 4. ORTEP drawing of asymmetric unit of compound 5 with numbering scheme.

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N. Muhammad et al. / Inorganica Chimica Acta 362 (2009) 2842–2848
Fig. 5. The ID chain structure of compound 5, propagation via O ? Sn Coordination.
Sn–O interaction. These bond lengths are in agreement with the
reported triorganotin(IV) carboxylates [37]. The intermolecular
C@O ? Sn coordination, in both compounds, leads to infinite zig-
zag chains containing the Sn centers and carboxylate groups as
shown in Figs. 3 and 5. The crystal data, selected bond lengths
and bond angles are given in Tables 1, 3 and 4.
bacteria. It was concluded that all complexes except 7 show higher
activity than the acid against different bacteria but were less active
than the standard drug. In present study, the diorganotin(IV) deriv-
atives are found to be more active than the triorganotin(IV) deriv-
atives. This situation is in sharp contrast to the earlier assessment
that an increase in the number of R groups on the tin(IV) atom en-
hances its biological activity. This anomalous behavior can be ex-
plained on the basis of the anionic ligand group that generally
plays a secondary role. In some cases however, it may also play
important role to enhance the biocidal activity of organotin(IV)
compounds [39].
4. Biological studies
4.1. Antibacterial
The synthesized complexes were tested for their antibacterial
activity, using the agar well diffusion method [38] and data are
listed in Table 5. The ligand was found to be inactive against all
4.2. Antifungal activity
The complexes were checked for antifungal activity against dif-
ferent plant pathogens by using the Agar tube dilution protocol
[38] and the data collected are listed in Table 6. Generally, all
derivatives show markedly higher antifungal activity than the li-
gand with few exceptions. Triorganotin(IV) derivatives are found
to be more active than the diorganotin derivatives, a behavior quite
consistent with the earlier report [40].
Table 3
Selected bond length (Å) And bond angles (°) of compound 4.
Bond length (Å)
Sn–O1
2.4682(17)
2.1778(15)
2.146(3)
Sn–C10
Sn–C14
O1–C1
2.139(2)
2.151(3)
1.238(3)
Sn–O2_b
Sn–C18
O2–C1
1.283(3)
4.3. Cytotoxicity
Bond angles (°)
O1–Sn–C10
O1–Sn–C14
O1–Sn–C18
O1–Sn–O2_b
C10–Sn–C14
C10–Sn–C18
83.22(7)
85.15(8)
87.47(9)
169.73(6)
115.6(1)
122.21(10)
C10–Sn–O2_b
C14–Sn–C18
C14–Sn–O2_b
C18–Sn–O2_b
Sn–O1–C1
87.11(7)
120.21(10)
95.98(8)
100.66(9)
150.94(14)
The complexes were also screened for cytotoxicity data, using
Brine-shrimp (Artemia salina) bioassay lethality method [38] and
results are shown in Table 7. The data illustrate that compounds
3, 4, 7 and ligand show no cytotoxicity. However, compounds 1,
2, 5 and 6 show low LD50 values in the range of 0.00–1.95
lg/ml
and exhibited significant toxicity.
Table 4
4.4. Anticancer activity
Selected bond length (Å) and bond angles (°) of compound 5.
The experimental conditions for in vitro anticancer assay
against prostate cancer cells (PC-3) of compounds 1, 2, 3, 5 and 7
are already described in the literature [41] and the activity of the
Bond length (Å)
Sn1–O2
Sn1–O4
Sn1–C19
Sn1–C20
Sn1–C21
O1–C1
2.2176(14)
2.3394(14)
2.126(3)
2.123(3)
2.122(2)
1.256(2)
O2–C1
1.273(2)
2.3318(14)
2.126(3)
2.127(3)
2.128(3)
2.2210(14)
Sn2 –O1
Sn2–C22
Sn2–C23
Sn2–C24
Sn2–O5_b
Table 5
Antibacterial bioassay resultsa,b for complexes 1–7 (inhibition zone in mm).
Bond angles (°)
O2–Sn1–O4
Imipinemb
176.01(5)
90.19(8)
92.50(8)
87.02(8)
89.13(8)
126.51(10)
94.94(8)
85.83(8)
115.96(10)
116.9(1)
O1–Sn2–C22
O1–Sn2–C23
O1–Sn2–C24
O1–Sn2–O5_b
C22–Sn2–C23
C22–Sn2–C24
C22–Sn2–O5_b
C23–Sn2–C24
C23–Sn2–O5_b
C24–Sn2–O5_b
83.62(7)
91.18(8)
87.74(8)
177.00(5)
115.43(10)
123.72(10)
93.53(7)
120.27(10)
90.87(8)
Bacterium
1
2
3
4
5
6
7
O2–Sn1–C19
O2–Sn1–C21
O4–Sn1–C20
O4–Sn1–C21
C20–Sn1–C21
O2–Sn1–C20
O4–Sn1–C19
C19 –Sn1–C21
C19–Sn1–C20
Eschericha coli
Bacillus subtilis
Shigella flexenari
Staphylococcus aureus
Pseudomonas aeruginosa
Salmonella typhi
12
17
13
15
14
16
20
20
19
20
10
11
16
13
12
11
17
12
14
16
20
26
30
37
36
26
32
30
16
10
12
11
10
17
a
Concentration used: 1 mg/ml of DMSO, Size of well: 6 mm (diameter).
Standard drug, dash indicate inactivity.
93.12(8)
b

N. Muhammad et al. / Inorganica Chimica Acta 362 (2009) 2842–2848
2847
g/ml)
Table 6
Antifungal bioassay results
a,b,c
for complexes 1–7.
Fungus
Inhibition (%)
Standard drugs
MIC (l
1
2
3
4
5
6
7
Candida albicans
Aspergillus flavus
Microsporum canis
Fusarium solani
Candida glabrata
10
20
40
10
30
80
70
50
60
90
80
90
90
70
80
90
60
70
80
60
Miconazole
AmphotericinB
Miconazole
Miconazole
Miconazole
110.8
20
98.25
73.25
110.8
20
30
40
80
a
Concentration of sample = 400
Incubation period = 7 days.
Incubation temperature = 27 °C.
l
g/ml of DMSO.
b
c
Table 7
Cytotoxicity dataa,b of compounds 1–7.
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1
2
3
4
5
6
7
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